Study: Factor XIII Deficiency More Prevalent in Patients Receiving Tocilizumab

Participants receiving tocilizumab therapy for rheumatoid arthritis were more likely to have acquired factor XIII deficiency than those receiving other therapies.

Rheumatoid arthritis (RA) patients receiving treatment with tocilizumab may be at risk for deficiency of a blood component associated with clotting and immune response, the results of a study published in the August 2013 edition of PLoS One suggest.

“In our study, only the tocilizumab-treated RA patients exhibited decreased plasma factor XIII activity levels among those treated with or without biologics,” the researchers noted. “ . . . We suppose that acquired factor XIII deficiency caused by tocilizumab results from the quantitative reduction of factor XIII in the plasma. Tocilizumab possibly suppresses the production of F[actor]XIII-A and/or F[actor]XIII-B in platelets, megakaryocytes, monocytes/macrophages and/or hepatocytes.”

Researchers decided to investigate a potential connection between the biologic therapy and factor XIII activity level after encountering a patient diagnosed with intrapelvic hematoma who presented to a Japanese hospital. The patient had received tocilizumab therapy for RA for at least 2 years, had no history of bleeding tendency or disorder related to bleeding, or history of trauma, but had a reduced factor XIII activity level at presentation, the researchers noted.

The patient’s factor XIII activity level remained low after 6 months of recovery, although it increased from 58% to 64%, the researchers added.

The research included 40 participants with RA and 19 healthy control patients. The participants with RA were divided into 3 groups based on therapy, and included 10 participants receiving methotrexate and no biologic therapies, 15 participants treated with tumor necrosis factor (TNF) inhibitors, and 15 participants treated with tocilizumab.

Participants in the tocilizumab group tended to have lower levels of factor XIII than participants in the control, methotrexate, and TNF groups. In addition, 73% of the participants receiving tocilizumab had factor XIII activity levels below the 70% lower limit, the researchers noted.

The researchers then decided to analyze factor XIII concentrations in plasma in the TNF and the tocilizumab groups, to determine how plasma concentrations correlated to activity levels. The results showed a positive correlation between factor XIII plasma concentrations and activity levels, and also showed a statistically significant difference between plasma concentration levels in the 2 treatment groups.

Despite the researchers’ findings, they found higher disease activity levels in participants treated without biologic therapies than in the participants receiving tocilizumab. In addition, a higher proportion of participants receiving TNF inhibitors received concomitant methotrexate than the participants receiving tocilizumab. The researchers’ findings imply that tocilizumab use and male gender were independent risk factors associated with factor XIII deficiency, which they did not detect in similar participants in the TNF group.

The researchers also detected no statistically significant relationships between factor XIII activity levels and age, duration of RA, history of treatment with biologic agents, dose of glucocorticosteroids, and concomitant use of methotrexate.