Author Topic: Older MS drugs {Novantrone, Imuran, Cytoxan] may boost cancer risk  (Read 144 times)

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Offline agate

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From MedPage Today, August 14, 2017:

Older MS Drugs May Boost Cancer Risk

But MS alone doesn't raise cancer risk, Sicilian study finds

 by Thomas Walsh, MedPage Today Intern

Patients with multiple sclerosis who took older immune suppressors had an increased risk of cancer, data from a Sicilian study showed.

In a single-center cohort, MS patients exposed to three older immunosuppressant drugs -- azathioprine (Imuran), mitoxantrone (Novantrone), and cyclophosphamide (Cytoxan) -- had a significantly greater risk of cancer compared with those not exposed (HR 11.05, 95% CI 1.67-73.3, P=0.013), Paolo Ragonese, MD, of the University of Palermo in Italy and colleagues, reported online in BMC Neurology.

The risk seemed to be driven by azathioprine and mitoxantrone, as there were no cancer deaths in those treated with cyclophosphamide in this study, the researchers said.

Even though newer drugs that are thought to have a better safety profile are now on the market, there are still MS patients "who do not respond to available drugs and experience an unfavorable disease course, rapidly accumulating disability, or patients who have lack of tolerance and need therefore a therapeutic alternative," the researchers wrote.

"In all of these patients, a strict long-term follow-up must be planned to avoid life-threatening conditions," they said.

Ragonese and colleagues studied 531 MS patients exposed to immune suppressants from 1994 to 2011 for a mean of nine years, and compared them with 531 MS patients who didn't take these drugs. Both MS groups consisted of 346 women and 185 men between ages 18 and 54. The researchers also compared cancer incidence in MS patients with cancer incidence in the general population of Sicily in similar age groups.

They found that those treated with azathioprine (median exposure 5 years) or mitoxantrone (median exposure 1 year) had a fourfold increased risk of cancer compared with MS patients who were not exposed. Among 346 patients treated with azathioprine, seven developed cancer in various sites (three breast, two gut, one brain, one ovary). Among 262 patients treated with mitoxantrone, six developed cancer (three leukemia, one gut, one lung, one pancreas).

"The association between the exposure to mitoxantrone and various forms of adult onset leukemia has been seen across Italy and elsewhere," said Jerry Wolinsky, MD, of the McGovern Medical School at UTHealth in Houston, who was not involved in the study. "That, plus its cardiotoxicity, has resulted in limiting the total dose that's supposed to be given and the fact that mitoxantrone came and went on the therapeutic horizon fairly quickly."

There was no association between cancer and cyclophosphamide exposure, but this accounted for the smallest group and follow-up wasn't as long, the researchers noted.
When compar[ed] with the general Sicilian population, MS patients on immunosuppressants had a fourfold higher rate of cancer -- but there was no difference in cancer incidence for MS patients who didn't take the drugs, they found. (SIR 0.97, CI 0.96-0.98). This is consistent with data found in other national registries, Wolinsky said.
Jeffrey Cohen, MD, of the Cleveland Clinic, who wasn't involved in the study, said it makes the "important point that the risk of cancer does not appear to be increased by MS alone."

The study was limited because the authors couldn't account for confounding environmental risk factors for cancer like smoking, given the data available. Also, all subjects were from the same geographic area, which could limit the applicability of the results to groups outside of Sicily.

At the same time, however, the results could apply to patients without MS who take these drugs. Azathioprine is still used in patients with neuromyelitis optica, and neurologists should be cautious with this population, said Jonathan Howard, MD, of New York University, who was not involved with the study.

Mitoxantrone and azathioprine are also more commonly used in patients with rheumatologic disorders, particularly rheumatoid arthritis, and other conditions of unknown etiology like sarcoidosis, Wolinsky noted.

Ragonese disclosed financial relationships with Merck Serono, Biogen, Novartis, Sanofi Genzyme, and Teva.

Co-authors disclosed financial relationships with Boehringer Ingelheim, Biogen, Teva, Merck Serono, and Novartis.

Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

The article can be seen here.
MS Speaks--online for 14 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Generic Copaxone (glatiramer acetate) 40mg 3 times/week since 12/16/20.


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