Wegener’s Granulomatosis Treatment Today

Abatacept: The presence of activated T lymphocytes within WG lesions has raised the question as to whether interference with costimulation could modulate disease. The Vasculitis Clinical Research Consortium is currently conducting a pilot study investigating abatacept in mild relapsing WG. There has been no experience with abatacept in WG to date, and this should not be used in clinical practice.

Figure 2: Pulmonary involvement can have many radiographic presentations, including single or bilateral nodules or infiltrates, cavities, or ground glass infiltrates suggestive of alveolar hemorrhage

Monitoring and Toxicity Prevention

Monitoring for disease activity and medication toxicity is among the most important aspects of care in a patient with WG. The type and frequency of monitoring will depend largely on the medications the patient receives (see Table 1, p. 19). Monitoring blood counts to prevent neutropenia and maintain the absolute neutrophil count above 1500/mm3 lessens the risk of infection-related morbidity and mortality that can occur from bacterial and opportunistic pathogens. For patients who do not have blood in their urine, self–urine dipstick testing can help detect new hematuria as an early indicator of renal disease.

For patients with pulmonary disease, perform chest imaging one month after the initiation of induction treatment to confirm improvement, at the time of transition to maintenance therapy, and every three to six months thereafter. For patients who do not have pulmonary disease, perform imaging every six to 12 months or for new symptoms.

The Future

There is much we have left to learn about WG; understanding disease pathophysiology plays a critical role in future innovations. Gaining a greater knowledge of disease mechanisms will allow those in the field to make informed decisions when planning novel clinical trials.

In 2008, there is much that physicians can offer WG patients—this includes not only our current treatment and monitoring strategies but also hope for the many advances to come.

Dr. Langford is director of the Center for Vasculitis Care and Research and associate professor of medicine at Cleveland Clinic in Cleveland, Ohio.

References

1. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: An analysis of 158 patients. Ann Intern Med. 1992;116:488–498.
2. Merkel PA, Lo GH, Holbrook JT, et al. High incidence of venous thrombotic events among patients with Wegener granulomatosis: The Wegener’s Clinical Occurrence of Thrombosis Study. Ann Intern Med. 2005;142;620–626.
3. Bosch X, Guilabert A, Font J. Antineutrophil cytoplasmic antibodies. Lancet. 2006;368; 404–18.
4. Finkielman JD, Merkel PA, Schroeder D, et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med. 2007;147:611–619.
5. Jennette JC, Xiao H, Falk RJ. Pahtogenesis of vascular inflammation by anti-neutrophil cytoplasmic antibodies. J Am Soc Nephrol. 2006;17:1235–1242.
6. Stone JH, Hoffman GS, Merkel PA, et al. A disease-specific activity index for Wegener’s granulomatosis: Modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides. Arthritis Rheum. 2001;44:912–920.
7. Molloy ES, Langford CA. Advances in the treatment of small vessel vasculitis. Rheum Dis Clin North Am. 2006;32:157–172.
8. Talar-Williams C, Hijazi YM, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med. 1996;124: 477–484.
9. De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:2461–2469.
10. Jayne D, Rasmussen N, Andrassy K, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349:36–44.
11. Langford CA, Talar-Williams C, Barron KS, Sneller MC. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener’s granulomatosis: Extended follow-up and rate of relapse. Am J Med. 2003;114:463–469.
12. Langford CA, Tallar Williams C, Sneller MC. Mycophenolate mofetil for remission maintenance in the treatment of Wegener’s granulomatosis. Arthritis Rheum. 2004;51: 278–283.
13. Metzler C, Miehle N, Manger K, et al. Elevated relapse rate under oral methotrexate versus leflunomide for maintenance of remission in Wegener’s granulomatosis. Rheumatology (Oxford). 2007;46:1087–1091.
14. Stegeman CA, Cohen Tervaert JW, de Jong PE, Kallenberg CG. Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. N Engl J Med. 1996;335:16–20.
15. Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18:2180–2188.
16. Wegener’s Granulomatosis Trial Research Group. Etanercept plus standard therapy for Wegener’s granulomatosis. N Engl J Med. 2005;352:351–361.
17. Stone JH, Holbrook JT, Marriott MA, et al. Solid malignancies among patients in the Wegener’s Granulomatosis Etanercept Trial. Arthritis Rheum. 2006;54:1608–1618.
18. Keogh KA, Wylam ME, Stone JH, Specks U. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52:262–268.
19. Keogh KA, Ytterberg SR, et al. Rituximab for refractory Wegener’s granulomatosis: Report of a prospective, open-label pilot trial. Am J Respir Crit Care Med. 2006;173:180–187.