7
Adverse effects of therapy for ANCA-associated vasculitis

https://doi.org/10.1016/j.berh.2009.04.002Get rights and content

The introduction of cyclophosphamide- and prednisolone-based treatment regimens has significantly improved outcome in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis. However, these regimens are nonspecific immunosuppressants associated with significant toxicity, including increased risk of infection, leucopenia, diabetes and malignancy. In addition, disease damage, particularly renal failure, increases the risk of toxicity. Improvements in disease management should include the increased awareness of treatment-related toxicity and its prevention.

Section snippets

Treatment strategies

Treatment of ANCA-associated vasculitis has an initial phase aimed at inducing remission and a second phase aiming to maintain remission and prevent relapse. Standard induction therapy with prednisolone and cyclophosphamide can induce remission in up to 90% of patients; maintenance therapy limits relapse rates to 18–40% [2]. The European League Against Rheumatism (EULAR) have recently published a series of guidelines on the management of vasculitis, with treatment recommended according to

Thromboembolic complications

The risk of thromboembolic disease is increased during inflammatory disease. Like other chronic inflammatory autoimmune diseases, such as systemic lupus erythematosus (SLE) or inflammatory bowel disease, the risk of deep vein thrombosis or pulmonary embolism is increased in patients with AASV. Studies of patients with AASV suggest an increased incidence of venous thromboembolism (VTE) of 1.8–7.0 out of 100 person-years, compared with 0.3 out of 100 person-years in the equivalent healthy Swedish

Drug reactions and hypersensitivity

At the outset of treatment with immunosuppressives, there are immediate risks related to drug toxicity, some of which can be difficult to distinguish from the effects of active or refractory disease.

Chronic burden of therapy

As patients with AASV increasingly survive the initial months and first year of their disease, they face the long-term effects of damage due to disease and therapy. In this phase, most adverse effects threaten function and quality of life rather than life itself; however, accumulated effects such as increasing risks of cardiovascular and malignant disease can slowly impact mortality in the longer term. One study of accumulated damage in WG reported that 15% of damage items were attributed to

Reducing the burden of therapy

The key to reducing the adverse effects of vasculitis therapy is better understanding of the disease, therefore allowing the use of less toxic therapies. Maintaining expertise in a rare disease is challenging and it is for this reason that a new set of recommendations by EULAR first recommends that patients with small and medium vessel vasculitis be managed in collaboration with centres of expertise [3]. This allows easier distinction between active disease and damage, enables ready access to

References (68)

  • Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel...
  • K. de Groot et al.

    The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review

    Nephrol Dial Transplant

    (2001)
  • D.R. Jayne et al.

    Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis

    J Am Soc Nephrol

    (2007)
  • K. De Groot et al.

    Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis

    Arthritis Rheum

    (2005)
  • D. Jayne et al.

    A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies

    N Engl J Med

    (2003)
  • Flossmann O, Jayne DR. Maintaining remission in a patient with...
  • G. Anderson et al.

    Wegener's granuloma. A series of 265 British cases seen between 1975 and 1985. A report by a sub-committee of the British Thoracic Society Research Committee

    Q J Med

    (1992)
  • G.S. Hoffman et al.

    Wegener's granulomatosis: patient-reported effects of disease on health, function, and income

    Arthritis Rheum

    (1998)
  • E. Reinhold-Keller et al.

    An interdisciplinary approach to the care of patients with Wegener's granulomatosis: long-term outcome in155 patients

    Arthritis Rheum

    (2000)
  • L. Harper et al.

    ANCA-associated renal vasculitis at the end of the twentieth century – a disease of older patients

    Rheumatology (Oxford)

    (2005)
  • A.S. Fauci et al.

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

    Ann Intern Med

    (1983)
  • L. Guillevin et al.

    A prospective, multi-centre randomised trial comparing steroids and pulse cyclophosphomide versus steroids and oral cyclophosphomide in the treatment of generalised Wegener's granulomatosis

    Arthritis Rheum

    (1997)
  • G.S. Hoffman et al.

    Wegener's granulomatosis: an analysis of 158 patients

    Ann Int Med

    (1992)
  • Etanercept plus standard therapy for Wegener's granulomatosis

    N Engl J Med

    (2005)
  • Charlier C, Henegar C, Launay O, et al. Risk factors for major infections in Wegener's granulomatosis: analysis of 113...
  • D.F. Battafarano et al.

    Antigen-specific antibody responses in lupus patients following immunization

    Arthritis Rheum

    (1998)
  • Holvast A, Stegeman CA, Benne CA, et al. Wegener's granulomatosis patients show an adequate antibody response to...
  • P.M. Stassen et al.

    Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis

    Nephrol Dial Transplant

    (2008)
  • B. Hellmich et al.

    G-CSF treatment for cyclophosphamide-induced severe neutropenia in Wegener's granulomatosis

    Arthritis Rheum

    (1999)
  • F.P. Ognibene et al.

    Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis

    Am J Respir Crit Care Med

    (1995)
  • M.M. Ward et al.

    Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality

    Arthritis Rheum

    (1999)
  • M.E. Falagas et al.

    Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review

    Clin Rheumatol

    (2007)
  • B. Godeau et al.

    Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases

    J Rheumatol

    (1994)
  • C.F. Thomas et al.

    Pneumocystis pneumonia

    N Engl J Med

    (2004)
  • Cited by (0)

    View full text