Patients drop MS drug, face relapse risk

A study of discontinuing natalizumab for multiple sclerosis patients testing positive for JC virus antibody found a higher relapse rate within 6 months than for patients continuing the drug whether positive or negative for JCV antibody.

Multiple sclerosis patients treated with natalizumab were more likely to discontinue therapy after learning of a positive JCV antibody result, only to see a higher risk for relapse, according to a small, single-center study.

Of nine patients who discontinued natalizumab (Tysabri) after learning their antibody result, which indicated a heightened risk for progressive multifocal leukoencephalopathy (PML) — a rare but life-threatening event — five relapsed within 6 months, said Denise Cheng, RN, of Winthrop Comprehensive MS Care Center in Mineola, N.Y.

These patients may have assumed their MS was no longer active, as opposed to a continuing disease process that was suppressed by the natalizumab treatment, Cheng said at the American Academy of Neurology’s annual meeting.

Four of the five patients resumed natalizumab after relapsing, she added. Three of them, as well as another patient who had persisted with substitute therapy despite the relapse, remained worse in terms of functional status than before natalizumab was initially discontinued.

PML, which is caused by reactivation of latent JC virus infection, has been seen in about 0.1% of MS patients receiving natalizumab. The risk is very low in patients without previous infection, but is more than 1% in patients with JC virus who take the drug for more than 2 years, and are taking other immunosuppressant agents.

In January, the FDA approved a serological test for JC virus exposure to be used in patients taking or considering natalizumab therapy.

Patients are now routinely tested for JCV antibodies before starting on natalizumab, with the risks and potential benefits explained to those with positive results, Cheng explained.

But patients already taking natalizumab are now being offered the test, and their decision-making and clinical outcomes are a matter of significant interest to neurologists.

She reported results in 71 patients at Winthrop tested for JCV antibody. Of these, 39 were negative and continued on natalizumab. There were two relapses during 6 months of follow up.

Among the 32 with positive test findings, 23 decided to stay on natalizumab, Cheng said. One of these suffered a relapse during follow up.

Of the nine patients who switched away from natalizumab, seven chose injectable drugs including interferon-beta products, glatiramer acetate (Copaxone), or rituximab (Rituxan). Two chose the oral drug fingolimod (Gilenya).

Cheng said patients underwent a three-month washout period after stopping natalizumab.

The four who did not relapse all had picked injectable agents for the substitution, Cheng said.

Both of the patients choosing fingolimod had relapses, including one who stayed with it even after suffering a relapse.

“She refused, absolutely refused, to go back on an injectable,” Cheng said.

The other patient choosing fingolimod could not tolerate the drug and had stopped it after 6 weeks and he had a mild relapse 2 weeks later.

Most of the relapsed patients had good results with natalizumab before discontinuing. One had a mild relapse after 20 infusions, and another experienced a moderate relapse after 11 infusions. The other three had no relapse while on the drug.

She suggested that it would be helpful to have an objective test to show that natalizumab is still exerting an effect in patients without clinical or radiological signs of disease. Such a test, she said, might “prevent the false conclusion that the MS had become quiescent.”

For patients considering natalizumab treatment, Cheng added, the JC virus antibody test was a valuable tool. Negative results in her clinic do not seem to make patients more likely to start the drug, she said, but it definitely increases the comfort level in those who do.

The study had no external funding.

Cheng reported having received payments from Biogen Idec, Bayer, and the MSAA.

Primary source: American Academy of Neurology

Source reference:

Gottesman M, et al “JCV antibody status: patient decision making and clinical course” AAN 2012; Abstract P02.140.