Can the use of with tofacitinib or tumor necrosis factor inhibitors (TNFi) affect the risk of cancer development in patients with rheumatoid arthritis?

This study investigated the occurrence and baseline risk factors of cancer occurrence in patients with rheumatoid arthritis (RA) treated with tofacitinib (Xeljanz) or tumor necrosis factor inhibitors (TNFis). The data showed a higher risk of cancer development with tofacitinib treatment compared to TNFis in these patients. 

RA is a chronic, inflammatory disease that affects the joints. It has been shown that RA also increases the risk of patients developing certain cancers. Most medications used for RA suppress the immune system. Long-term use of disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) may increase the risk of cancer development in patients.

Biological DMARDs (bDMARDs) such as tofacitinib and TNFis such as adalimumab (Humira) and etanercept (Enbrel). The use of bDMARDs and non-steroidal anti-inflammatory drugs may reduce the risk of cancer development for patients with RA. However, risk factors for cardiovascular (CV) disease can also increase the risk of patients developing cancer. There is a need to address links between baseline risk factors, CV risks, and cancers in patients with RA treated with tofacitinib and TNFis.

This study included 4362 patients with RA. Patients had at least one additional CV risk factor. Patients were randomly assigned to 5 groups. Group 1 received either tofacitinib or a TNFi. Patients were followed for an average of 44 months. 

Overall, the risk of cancer was higher for the tofacitinib group compared to the TNFi group. There was a higher risk of lung cancer with 10 mg of tofacitinib, twice daily compared with TNFi. In patients treated with TNFis, the most common cancer reported was breast cancer. 

Current or past smokers had slightly higher risks of developing cancer compared to those who never smoked. The highest occurrence of cancer was among patients with a history of atherosclerotic CV disease or those with high baseline CV risk scores. Overall, over 66 months, more than 93% of patients did not develop any cancers. 

The study concluded that there was an increase in the risk of cancers with the use of tofacitinib compared with TNFi in patients with RA. 

The study was not designed to draw firm conclusions and these results are considered as exploratory. Additionally, there was no standard approach for screening, staging, and grading the cancers across study sites.