Treatment of Wegener's granulomatosis with intermittent high-dose intravenous cyclophosphamide

doi:10.1016/0002-9343(90)90367-M

The American Journal of Medicine

Volume 89, Issue 4, October 1990, Pages 403-410

https://doi.org/10.1016/0002-9343(90)90367-M Get rights and content

Abstract

purpose: Concerns regarding the long-term toxicity of daily cyclophosphamide (CP) therapy for the systemic vasculitides have led us to evaluate alternative approaches to treatment in an attempt to achieve comparable efficacy with less toxicity. This study sought to determine the efficacy, toxicity, and immunologic effects of glucocorticoids (GC) and intermittent high-dose intravenous CP (“pulse” CP) in the treatment of 14 patients with Wegener's granulomatosis (WG).

patients and methods: The diagnosis of active WG was supported by a typical clinical presentation and histopathologic findings of vasculitis, granulomatous inflammation, and tissue necrosis. GC treatment was initially provided on a daily basis and later tapered to an alternate-day schedule if vasculitis remained inactive. Pulse CP treatment was initially administered once a month for 6 months. If after 6 months remission had been attained and GC therapy had been discontinued, then pulse CP treatment was given at less frequent intervals thereafter. Treatment and evaluation were provided for participants as inpatients in a clinical research center (National Institutes of Health).

results: Thirteen of 14 patients (93%) initially experienced unequivocal improvement with pulse CP therapy, and seven of 14 (50%) achieved remission within 4 months. However, treatment was associated with significant toxicity in two patients and later relapses in nine patients, so that a total of 79% either failed to achieve sustained remission or were unable to continue therapy. Three of 14 (21%) patients have achieved sustained remissions with the pulse CP protocol and one additional patient (who had a limited exacerbation of WG) continues to receive that therapy after 14 to 22 months (mean 17 months).

conclusions: The use of pulse CP and GC therapy in 14 patients with WG was associated with a high initial response rate. However, failure to respond initially to treatment, to sustain improvement, or to tolerate continued treatment was noted in 79% of patients within a period of 1 to 22 months. These observations indicate that this particular pulse CP protocol does not achieve a high degree of lasting efficacy.

References (25)

ES Leib et al.
Immunosuppressive and corticosteroid therapy in polyarteritis nodosa
Am J Med
(1979)
AS Fauci et al.
Cyclophosphamide therapy of severe systemic necrotizing vasculitis
N Engl J Med
(1979)
AS Fauci et al.
Wegener's granulomatosis: studies in eighteen patients and a review of the literature
Medicine (Baltimore)
(1973)
AS Fauci et al.
Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years
Ann Intern Med
(1983)
AS Fauci et al.
The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations
Ann Intern Med
(1978)
MJ Reza et al.
Wegener's granulomatosis
JE Balow et al.
Effect of treatment on the evaluation of renal abnormalities in lupus nephritis
N Engl J Med
(1984)
JE Balow et al.
Lupus nephritis
Ann Intern Med
(1987)
HA Austin et al.
Therapy of lupus nephritis
EW Walton
Giant cell granuloma of the respiratory tract (Wegener's granulomatosis)
Br Med J
(1958)

D Hollander et al.

The use of alkylating agents in the treatment of Wegener's granulomatosis

Ann Intern Med

(1967)

DA Berman et al.

Wegener's granulomatosis

Cited by (206)

Whitcup and Nussenblatt’s Uveitis: Fundamentals and Clinical Practice
2021, Whitcup and Nussenblatt's Uveitis: Fundamentals and Clinical Practice
Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Is There Still a Role for Cyclophosphamide?
2019, Rheumatic Disease Clinics of North America
Citation Excerpt :
Another study in the same population calculated a 31-fold increased risk for bladder cancer at any age and 51-fold in patients younger than 65 years old compared with the general population.13 In an effort to reduce side effects associated with oral CYC, studies comparing use of pulse intravenous (IV) CYC showed comparable rates to that of oral CYC; however, relapse rates were higher.12,14,15 The Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis trial compared pulse IV every 2 weeks to 3 weeks with daily oral CYC for induction of CR in AAV, showing similar rates in achievement of CR (88.1% with IV and 87.7% with orally) as well as the time to remission, relapse rates, cumulative doses of GCs, and deaths.
Granulomatosis with polyangiitis (Wegener's granulomatosis) causing atlantoaxial instability: a case report
2016, Spine Journal
Citation Excerpt :
In patients with GPA, treatment with glucocorticoids and cyclophosphamide results in significant improvement in 91% of affected patients, complete remission in 75%, and an overall survival rate of 80% over 24 years following diagnosis [4].
No previous cases of atlantoaxial instability due to granulomatosis with polyangiitis have been reported.
The aim of this study was to report a case of granulomatosis with polyangiitis causing atlantoaxial instability.
This is a case report.
A 45-year-old woman participated in this study.
The patient's pain and atlantoaxial instability were resolved.
A 45-year-old Caucasian woman with a large ulcerative lesion in her oropharynx initially presented with chronic sinusitis, pharyngitis, and severe odynophagia. Years after her original symptoms began, she developed neck pain radiating into her upper trapezial region and shoulders.
Atlantoaxial fusion was performed on the patient, resolving her neck, upper trapezial, and shoulder pain. She was diagnosed with granulomatosis with polyangiitis (formerly Wegener's granulomatosis) and treated with cyclophosphamide.
Granulomatosis with polyangiitis should be part of the working differential diagnosis for non-traumatic cervical spine injury. The atlantoaxial instability can be managed with stabilization, and the disease process itself can be treated with cyclophosphamide.
Pharmacology and Drug Therapy: Nonbiologic Therapies
2015, Textbook of Pediatric Rheumatology
Pharmacology and drug therapy
2011, Textbook of Pediatric Rheumatology
Treatment of ANCA-associated systemic vasculitis
2010, Reumatologia Clinica
El tratamiento de las vasculitis sistémicas ha experimentado cambios sustanciales en los últimos años. La ciclofosfamida sigue teniendo un papel crucial en la inducción de remisión en formas severas, reduciendo considerablemente la mortalidad. Sin embargo, su empleo conlleva una importante toxicidad a largo plazo y el acúmulo de morbilidad derivada de un control subóptimo del proceso. Se han desarrollado estrategias para limitar la exposición al fármaco y minimizar su toxicidad, como son el uso de pulsos endovenosos como alternativa a la vía oral y la estrategia secuencial. Tanto para inducir remisión en casos no severos como para el mantenimiento de remisión se preconiza el empleo de inmunosupresores alternativos, como son el metotrexate, la azatioprina o la leflunomide. En determinadas situaciones con compromiso vital puede recurrirse a opciones como la plasmaféresis o las inmunoglobulinas endovenosas. Las terapias biológicas suponen una alternativa prometedora, si bien su empleo actual debe restringirse a los casos refractarios.
The treatment of systemic vasculitis has undergone important changes in recent years. Cyclophosphamide still plays a crucial role in the induction of remission in severe forms, reducing the mortality. However, its use entails a significant long-term toxicity and the accumulation of damage resulting from a sub-optimal control of the process. Strategies has been developed to limit exposure to the drug and minimize its toxicity, such as using intravenous pulses as an alternative to oral administration and a sequential strategy. Both induce remission in less severe cases and work also for the maintenance of remission; the use of alternative immunosuppressants, such as methotrexate, azathioprine or leflunomide has been advocated. In life-threatening situations, options such as plasmapheresis or intravenous inmunoglobulins are available. Biologic therapies are a promising alternative, but their use must be limited for now to refractory cases.

View all citing articles on Scopus

View full text

Clinical studyTreatment of Wegener's granulomatosis with intermittent high-dose intravenous cyclophosphamide

Abstract

Am J Med

Cyclophosphamide therapy of severe systemic necrotizing vasculitis

N Engl J Med

Wegener's granulomatosis: studies in eighteen patients and a review of the literature

Medicine (Baltimore)

Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years

Ann Intern Med

The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations

Ann Intern Med

Wegener's granulomatosis

Effect of treatment on the evaluation of renal abnormalities in lupus nephritis

N Engl J Med

Lupus nephritis

Ann Intern Med

Therapy of lupus nephritis

Giant cell granuloma of the respiratory tract (Wegener's granulomatosis)

Br Med J

The use of alkylating agents in the treatment of Wegener's granulomatosis

Ann Intern Med

Wegener's granulomatosis

Clinical study
Treatment of Wegener's granulomatosis with intermittent high-dose intravenous cyclophosphamide