After a conducting a large meta-analysis of clinical trials involving more than 29,000 patients, researchers from the University of Texas MD Anderson Cancer Center in Houston have concluded that patients taking currently available biologic therapies for their rheumatoid arthritis (RA) are not at increased risk of cancer, compared with those receiving traditional disease-modifying treatments for RA, such as methotrexate and anti-inflammatory drugs.
The study, led by Maria E. Suarez-Almazor, MD, from MD Anderson’s Department of General Internal Medicine, was published online on September 5 in JAMA.
The worry over newer biologic response modifiers for RA is that several of them include tumor necrosis factor (TNF) inhibitors, which some studies have suggested increase the risk of developing certain malignancies, including spontaneous lymphoma in children and adolescents. All TNF inhibitors currently carry an FDA label warning against the risk of malignancy.
Biologic response modifiers, or BRMs, are used by about one-quarter to one-half of patients with RA, and are prescribed as second-line therapy when traditional treatments for RA fail to provide a benefit. BRMs target secretions in the joints that can trigger inflammation and lead to joint destruction. Because they also target immune cells, there has been some concern that they may pose a cancer risk.
Study Design and Findings
To evaluate malignancy risk in RA patients, Dr. Suarez-Almazor and colleagues searched electronic databases, conference proceedings, and websites of regulatory agencies for people with RA who were enrolled in randomized controlled trials of the nine BRMs currently approved by the US Food and Drug Administration (FDA) for use in RA (abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab), from study initiation through early July 2012. The studies included in the assessment had to compare the safety of any BRMs used in RA patients vs placebo and/or any traditional disease-modifying antirheumatic drugs, and needed to have at least 6 months of follow-up.
Independent reviewers selected studies and extracted data on quality and outcomes. Dr. Suarez-Almazor and colleagues used the Cochrane Collaboration trials database to analyze a total of 63 randomized controlled trials with 29,423 patients, and found no statistically significant increased risk of developing malignancy in the RA patients receiving BRMs. They wrote that, of the 29,423 patients, 211 developed a malignancy during the trial. There were 118 solid tumors reported, 48 skin cancers, 14 lymphomas, 5 hematologic nonlymphomas, and 26 malignancies that were not specified. During the first year of therapy, they said, the incidence rate for any malignancy was very low in the BRM plus methotrexate group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65–0.92), in the BRM monotherapy group (HR, 0.64; 95% CI, 0.42–0.95), and in the controls (HR, 0.66; 95% CI, 0.52–0.84). Treatment with the BRM anakinra plus the traditional RA drug methotrexate showed lower odds than methotrexate given alone (Peto odds ratio, 0.11; 95% CI, 0.03–0.45). However, the investigators noted that while “no statistically significant risk was observed for specific cancer sites…the Peto odds ratio for lymphoma was 2.1 (95% CI, 0.55–8.4) in patients receiving tumor necrosis factor inhibitors compared with controls.”
“These results are reassuring for patients considering biologic therapies for their disease,” said Dr. Suarez-Almazor, commenting on the study in a news release from MD Anderson. “Patients are understandably concerned when treatments are linked to cancer risk. With this knowledge, clinicians can effectively demonstrate that the benefits of BRMs far outweigh the risk.”
Other researchers who contributed to the study are from the department of general internal medicine and the research medical library at MD Anderson; the Texas Tech University Health Science Center (based in Lubbock, Texas), the Spanish Society of Rheumatology (Madrid, Spain), the Hospital 12 de Octubre (Madrid); and Manati Medical Center (in Manati, Puerto Rico).