DESTIN, FLA. — Advances in biologic therapies have begun to change the treatment landscape for patients with systemic vasculitis, according to Dr. Philip Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.

“Biologics have led to the first new therapeutic option for patients with systemic vasculitis since cyclophosphamides became the standard of care in the 1970s,” Dr. Seo said at the meeting, which was sponsored by the Medical College of Virginia. “The most exciting thing to happen this past year has probably been the use of rituximab for Wegener's granulomatosis and microscopic polyangiitis.”

Preliminary results from the multicenter, randomized controlled RAVE (Rituximab for ANCA-Associated Vasculitis) trial, which were presented at the 2009 annual meeting of the American College of Rheumatology in Philadelphia, showed that the anti–B-cell agent rituximab was as effective as cyclophosphamide for these conditions, both of which are variants of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, Dr. Seo explained. Additionally, rituximab was superior to cyclophosphamide for patients who experienced severe disease flares, he said, noting that patients in the trial who were randomized to rituximab therapy experienced a near-complete depletion of B cells, which are ultimately the source of ANCA.

Rituximab may also be an important treatment option for patients with hepatitis C virus (HCV)–associated cryoglobulinemic vasculitis who do not respond to antiviral therapy, Dr. Seo said. About 5% of patients with HCV develop cryoglobulinemic vasculitis when their B lymphocytes produce abnormal proteins called cryoglobulins in response to the viral infection, he said. The resulting vasculitis may involve the skin, joints, kidneys, nerves, and other sites and can cause skin rashes, joint pain, weakness, fatigue, and numbness.

In an open-label, pilot study that was designed to assess the impact of combining rituximab with antiviral therapy, 16 patients with refractory HCV-related cryoglobulinemia were treated with weekly rituximab infusions for 4 weeks, combined with peginterferon plus ribavirin for 12 months (Ann. Rheum. Dis. 2008;67:1431-6). Of the 16 patients, 15 showed clinical improvement and 10 were complete responders, Dr. Seo said. “Nearly all of the patients had improvement in cutaneous ulcers, arthralgias, and purpura, and more than half had improvement in glomerulonephritis.”

In addition to anti–B-cell strategies, tumor necrosis factor blockade may have a therapeutic role in certain types of vasculitis as well, said Dr. Seo. For example, he said, in a recently reported case series of 25 patients with refractory Takayasu's arteritis, treatment with infliximab or etanercept for a median 28 months was associated with remission of the large-vessel vasculitis in a majority of the patients, which in turn resulted in the reduction or discontinuation of prednisone and other immunosuppressive drugs (Ann. Rheum. Dis. 2008;67:1567-9).

The role of biologic agents in the treatment of other forms of vasculitis is not yet clear, Dr. Seo said. For example, “although infliximab is effective for the treatment of Takayasu's, a trial [of the drug] in another large-vessel vasculitis, giant cell arteritis, was stopped due to lack of efficacy,” he said (Ann. Intern. Med. 2007;146:621-30). Also, a large study investigating the potential role of etanercept compared with cyclophosphamide and glucocorticoids in Wegener's granulomatosis showed no differences in the time to remission, frequency or duration of remission, frequency or severity of flares, or frequency or severity of adverse events (N. Engl. J. Med. 2005;352:351-61).

In all cases, “we have to proceed with caution, because the long-term consequences of [biologic] therapy are unknown, especially with rituximab and some of the newer agents coming down the pipe,” he warned.

“The TNF inhibitors may be associated with malignancy in some cases. Infliximab, in particular, is associated with a higher prevalence of malignancy in pediatric populations, and an increased risk of infection, including tuberculosis,” he said.

Regarding the anti–B-cell strategies, “the consequences of chronic B-cell depletion over years are largely unknown,” although studies have observed a decline in immunoglobulin levels in chronically treated patients, Dr. Seo said. Also, he noted, “rituximab may be associated with a relatively rare infection called progressive multifocal leukoencephalopathy.”

Biologics are clearly poised to become an important weapon in the fight against vasculitis, said Dr. Seo, “especially for patients in whom the cytotoxic drugs that we might normally use are contraindicated, such as older patients who might not be able to tolerate them, or patients who have already seen a cytotoxic agent maybe two or three times, who might not be able to tolerate it a fourth time.” Additionally, he said, “biologics may be well suited for younger patients, where you're concerned about fertility, because, unfortunately, about half of all patients on cytotoxic drugs will become infertile.”

Disclosures: Dr. Seo reported having no financial disclosures related to this presentation.

To watch a video interview of Dr. Seo, go to www.youtube.com/elsglobalmedicalnews

Biologics Have Advanced Therapy in Systemic Vasculitis