Arthritis Drugs May Not Be Complicit in Cancer Risks

BOSTON, Aug. 31 -- Concerns that disease-modifying antirheumatic drugs could increase the risk of malignancies may be unfounded, according to a review of U.S. and Canadian databases.

Patients with rheumatoid arthritis are known to be at higher risk than the general population for lymphoproliferative malignancies such as non-Hodgkin's lymphoma and multiple myeloma, as well as other cancers.

But whether the increased risk is linked to biologic disease-modifying antirheumatic drugs (DMARDs) such as tumor necrosis factor ? (TNF-?) antagonists or to RA itself is unclear, noted Soko Setoguchi, M.D., Dr.PH., of Brigham and Women's Hospital here, and colleagues, in the September issue of Arthritis & Rheumatism.

When they compared pooled data on more than 1,100 RA patients treated with TNF-? or interleukin-1 receptor antagonists with more than 7,306 RA patients treated with methotrexate, they found no significant differences in cancer risk between the groups.

"Our data indicate that it is unlikely that RA patients who have received biologic agents have a much greater risk of lymphoproliferative disorders, hematologic malignancies, and solid tumors compared with methotrexate users, " Dr. Setoguchi and colleagues wrote.

The authors acknowledged, however, that even with large data sets and pooled analyses, it's difficult to study the effects of relatively infrequent drug exposure on relatively rare diseases, and that further study of possible links between TNF-? antagonists and cancer risk is needed.

The investigators conducted a cohort pooling study using information from Medicare databases in New Jersey and Pennsylvania, and from a database of all adult residents of British Columbia.

They drew data on RA patients ages 65 and older with RA, 1,152 of whom had received a prescription for a DMARD, either the TNF-? inhibitors Enbrel (etanercept, 64%), Remicade (infliximab, 33%), or the IL-1 receptor inhibitor Kineret (anankinra, 2%).

Of the patients who were taking a DMARD, 55% had previously received methotrexate, and 39% were receiving methotrexate when they began taking one of the other agents. None of the patients in the cohort had a diagnosis of cancer at the start of the study.

The authors looked at medical utilization data as a surrogate for each patient's general health during the six months prior to exposure to either a DMARD or methotrexate.

They used time-varying propensity scores to adjust for a wide range of potential confounding factors, as well as stratified proportional hazards regression, to estimate the effects of disease modifying agents on cancer risk.

They study endpoints were hematologic malignancies (lymphoma, multiple myeloma, and leukemia), common solid tumors (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary tract/bladder, and melanoma).

The investigators identified a total of 11 hematologic malignancies and 46 solid tumors during 2,940 person-years of TNF-? or IL-1 receptor antagonist use, compared with 88 hematologic malignancies and 558 solid tumors during 30,300 person-years of methotrexate use.

Compared with methotrexate users, the hazard ratio for hematologic cancers among users of biologic disease-modifying agents was 1.37 (95% confidence interval, 0.71-2.65), and the hazard ratio for solid tumors was 0.91 (95% CI, 0.65-1.26).

The overall difference in estimated cancer risk was less than 5% between RA patients treated with a TNF? antagonist and those treated with methotrexate.

But "even with the use of a large combined data set, it is a challenge to investigate the effect of a relatively rare exposure (biologic disease-modifying antirheumatic drugs) on rare diseases (hematologic malignancies)," the authors wrote.

"Larger collaborative studies and/or longer followup will be needed in order to obtain more precise estimates," they concluded.

The research was partially supported by a grant from Novartis.