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Etanercept + CYC combo may increase cancer risks in Wegener’s Granulomatosis

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – The combination of etanercept and cyclophosphamide might be a risky one in patients with Wegener’s Granulomatosis, especially with those who have long-term, chronic disease, researchers reported in Arthritis & Rheumatism.

The report is a 5-year follow-up of the Wegener’s Granulomatosis Etanercept Trial (WGET), which found higher rates of solid cancers in patients who were treated with etanercept than those that received a placebo.

While the authors, led by Dr. Ulrich Specks of the Mayo Clinic in Rochester, Minn. found that etanercept did not carry a higher cancer risk than placebo after treatment had ended, they still conclude that it should be avoided in patients treated with cyclophosphamide (CYC).

In the current study, 153 of 180 patients from WGET were followed for a median 43 months. Just over half of those patients had been randomly assigned to treatment with the anti-tumor necrosis factor etanercept (25mg subcutaneously twice a week), the others to placebo — both in addition to standard therapy.

During the 30-month trial, solid cancers were diagnosed in 7% of patients assigned to etanercept and none in the placebo group (p = 0.01). Compared to age and sex-adjusted cancer rates for the U.S. population, the SIR for patients taking etanercept was 3.8.

Over the follow-up period, 13 new cases of solid cancers were diagnosed: 8 in the etanercept group and 5 in the placebo group.

All 13 patients diagnosed with cancer had also been treated with CYC.

While there was not a significant difference in cancer rates between the etanercept and placebo groups during follow-up, the overall cancer rate in patients taking etanercept was still significantly higher when the trial and follow-up periods were combined (18% vs. 7%, p = 0.03). SIRs were 3.76 in the etanercept group and 1.71 in placebo patients.

The finding “suggests that after discontinuation of etanercept the malignancy risk conferred by this agent in WG reverts back to the increased baseline inherent to the disease and its treatment,” Dr. Specks and colleagues write.

Compared to patients that didn’t get cancer during the follow-up, those with a cancer diagnosis had a longer duration of WG and had a higher frequency of cancer before the start of the trial. Patients were not included in WGET if they had cancer in the 5 years before the start of the trial.

The authors also said that there is no clear evidence that vasculitis on its own would increase the risk of cancer, and previous studies have suggested that the increased cancer risk seen in WG patients may be due to CYC exposure. Ten of 13 patients diagnosed with cancer during the follow-up had received more than 36g of CYC, they note.

Dr. Specks and his colleagues say the findings show the need for safer treatment for WG to decrease physicians’ reliance on CYC.

But for now, they conclude, “Because of the potential interaction between anti-TNF therapy and high CYC exposure in the development of malignancy and the lack of demonstrable efficacy in WG, is it reasonable to avoid the use of etanercept in patients with WG, particularly those with a history of chronic, relapsing disease, CYC exposure, or a previous history of malignancy.”

Arthritis & Rheumatism.