CHICAGO — Vasculitis is less likely to kill affected patients than are complications arising from the drugs used to treat it. So thinking about vasculitis in terms of disease activity and disease damage may help avoid overtreatment.
In vasculitis, damage occurs in two peaks. The first is the direct result of the vasculitis itself, such as pulmonary fibrosis and renal insufficiency that are the direct consequence of disease flare. The second peak results from the untoward effects of therapies such as cyclophosphamide and glucocorticoids that accumulate in patients over time, Dr. Philip Seo said at a symposium sponsored by the American College of Rheumatology.
This accumulation of damage actually predicts increased mortality and is important in the way clinicians think about their patients when deciding what to do next, said Dr. Seo, codirector of the Johns Hopkins Vasculitis Center in Baltimore.
“It's important to recognize in patients that there are manifestations that are clearly due to vasculitis that are not going to be amenable to immunosuppressive therapy, and really should not be treated as such,” he said. “Because the more immunosuppressive therapy you use, the more likely [patients] are to accrue damage as a consequence, and that just becomes an endless cycle.”
Data from the European Vasculitis (EUVAS) Study Group show that only 73% of patients with vasculitis were alive at 5 years. Impaired kidney function was a significant predictor of poor outcomes, whereas younger age was a clear benefit. Notably, vasculitis was not the No. 1 killer. The top three causes of death were infection, cardiovascular events, and malignancy, “all of which can relate back to the drugs we use to treat these patients,” said Dr. Seo, who reported no relevant conflicts of interest.
The WeCLOT (Wegener's Clinical Occurrence of Thrombosis) trial highlighted the increased risk of venous thromboembolism (VTE), reporting a VTE incidence rate of 7 per 100 person-years in 167 patients enrolled with active Wegener's granulomatosis and no prior VTE events (Ann. Intern. Med. 2005;142:620-5). To put this in context, patients with Wegener's are 23 times more likely than the general population to have a venous thromboembolic event and 7 times more likely to do so than patients with lupus, which is conventionally considered to be the prothrombotic disease, he said.
Perhaps less well known is the increased risk for solid malignancies. The 5-year follow-up data reported in 2008 from WGET (Wegener's Granulomatosis Etanercept Trial) showed a 4.4-fold increased risk of solid malignancies in patients with Wegener's who were treated with etanercept (Enbrel) and cyclophosphamide. It has been unclear whether this finding can be generalized beyond this population, but new unpublished data from 469 of 554 patients enrolled in the EUVAS Long-Term Follow-Up Study are moving in the same direction, Dr. Seo said. EUVAS investigators identified 31 solid malignancies (6.6%) including 8 prostate, 5 lung, and 4 bladder cancers, as well as 22 skin malignancies (3.8%).
Dr. Seo highlighted nasal blockade/chronic discharge/crusting (32%), hypertension (22%), hearing loss (20%), chronic sinusitis (12%), and osteoporosis (10%) as a short list of other common damage.