Bladder cancer risk not increased with pioglitazone therapy

Through an analysis of nearly 200,000 patients, no statistically significant increased risk for bladder cancer was found with the use of Actos, according to recent study findings published in JAMA.

Assiamira Ferrara, MD, PhD, of Kaiser Permanente Northern California, and colleagues conducted a bladder cancer cohort analysis of 193,099 people aged 40 years or older in 1997 to 2002 until December 2012; evaluated 464 case patients and 464 matched controls for additional confounders; and performed a cohort analysis for 10 additional cancers on 236,507 people aged 40 years or older in 1997 to 2005 until June 2012. All participants were members of Kaiser Permanente Northern California.

Assiamira Ferrara

The additional cancers included prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin’s lymphoma, pancreas, kidney/renal pelvis, rectum and melanoma.

Among the bladder cancer cohort, 34,181 participants received Actos (pioglitazone, Takeda) during follow-up. Overall, 0.65% of participants were diagnosed with bladder cancer. No significant association was found between ever use of pioglitazone and bladder cancer (HR = 1.06; 95% CI, 0.89-1.26).

Through the case-control analysis, researchers found similar rates of bladder cancer between ever use (19.6%) and nonusers (17.5%).

In the study analyzing additional cancers, 16% of participants had received pioglitazone by the end of follow-up. The researchers found no association between most of the cancers and pioglitazone use; however, there was an increased risk for prostate cancer (HR = 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR = 1.41; 95% CI, 1.16-1.71).

“There was no statistically significant increased risk of bladder cancer associated with pioglitazone use,” the researchers wrote. “However, a small increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether the observed associations are causal or due to change, residual confounding, or reverse causality.”

In an accompanying editorial, Joshua M. Sharfstein, MD, of Johns Hopkins Bloomberg School of Public Health, and Aaron S. Kesselheim, MD, JD, MPH, of Brigham and Women’s Hospital, wrote that the results “shed new light on the safety of pioglitazone reflecting the dynamic nature of many drug safety questions.

“As in this case, caution and further review are the appropriate responses to many safety signals,” they wrote. “But when emerging available data — clinical, laboratory, observational and even population-based studies — create a compelling picture of risk in excess of potential benefit to patients, the FDA should act to protect the public.”

In another editorial, Phil B. Fontanarosa, MD, MBA, executive deputy editor of JAMA, and colleagues wrote that medical journals have a responsibility to review studies evaluating the potential relationship between drugs, devices or vaccines and adverse outcomes.

“Even though no observational study examining the relationship between an exposure and an outcome can definitively establish ‘positive’ cause-and-effect results, and no observational study can definitively prove ‘negative’ results, each study adds to the totality of evidence regarding the safety of drugs, devices and vaccines,” they wrote. “By publishing the results of these studies, JAMA will continue to provide information physicians can use in discussions with patients and regulatory bodies can use in policy decisions about the benefits and risks of various therapies.”

References:

Fontanarosa PB, et al. JAMA. 2015;doi:10.1001/jama.2015.8232.

Lewis JD, et al. JAMA. 2015;doi:10.1001/jama.2015.7996.

Sharfstein JM, Kesselheim AS. JAMA. 2015;doi:10.1001/jama.2015.7151.

Disclosure: Ferrara reports financial ties with Sanofi-Aventis and Takeda Development Center Americas Inc. Kesselheim reports various financial ties with the FDA, Greenwall Foundation and the Harvard Program in Therapeutic Science. Fontanarosa and Sharfstein report no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.