Yervoy, Keytruda Linked To Muscoskeletal Immune-Related Adverse Event Problems: Study

Researchers warn that musculoskeletal problems may be common with Yervoy and Keytruda, after examining immune-related adverse event data linked to the cancer drugs. 

In a study published this month in the medical journal The BMJ, researchers with the Memorial Sloan Kettering Cancer Center in New York found that anti-programmed death 1 (anti-PD-1) medications, such as Keytruda and Yervoy, are linked to more organ specific immune-related adverse events when compared to other cancer treatments. They also indicated that inconsistent reporting of musculoskeletal problems may be hiding the fact that such problems are more common than believed.

Researchers looked at 13 studies that examined adverse events linked to Keytruda, Yervoy and other cancer drugs. They found that serious organ specific immune-related adverse events were rare, but when they compared the drugs to the use of standard treatments they found that the increased risk of hypothyroidism was seven times higher. They also found that the risk of pneumonitis was more than five times higher, and the risk of colitis and hypophysitis were three times higher with anti-PD-1 drugs.

The study also indicated that reports of musculoskeletal problems, such as arthraligia and back pain were inconsistently reported, with some studies revealing a 20% increased risk.

“Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments,” the researchers concluded. “Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common.”

Yervoy (ipilimumab) is  manufactured and sold by Bristol-Myers Squibb, for treatment of melanoma skin cancer.

A 2016 study by Johns Hopkins researchers also linked Opdivo and Yervoy to immune-related adverse events, which could manifest as inflammatory arthritis and sicca syndrome.

Other types of immune responses have been linked to the drugs, which strengthens the chances that the drugs can cause arthritis as well.

In August, the FDA issued a safety alert announcing that it had halted two other Keytruda clinical trials, KEYNOTE-183 and KEYNOTE-185 involving the use of Keytruda to treat multiple myeloma, due to a number of patient deaths.

In KEYNOTE-183, the FDA found that the use of Keytruda, in combination with dexamethasone and either of two immunomodulatory agents; lenalidomide or pomalidomide, led to a 61% increased risk of death. The agency found that 29 patients in the Keytruda arm of the clinical trial died, compared to only 21 deaths among the control patients, who did not receive the drug.

KEYNOTE-185’s results were even worse. That clinical trial, involving about 300 patients, saw an even higher risk, with more than twice as many Keytruda patients dying than those in the control group, 19 to 9. That trial also showed that 54% of the patients given a Keytruda-based drug combination had a 54% chance of severe adverse health effects, compared to only 39% in the control group.