Tumor necrosis factor alpha antagonist use and cancer in patients with rheumatoid arthritis.
OBJECTIVE
Concerns persist about a possible association between tumor necrosis factor alpha (TNFalpha) antagonist treatment and development of cancers in patients with rheumatoid arthritis (RA). This study was undertaken to estimate the association between treatment with biologic disease-modifying antirheumatic drugs (DMARDs) and development of cancer in patients with RA.


METHODS
We conducted a cohort study pooling administrative databases from 2 US states and 1 Canadian province. A cohort of patients who had received a diagnosis of RA on > or =1 occasion and had been prescribed DMARDs was identified. We categorized patients with a prescription for a biologic DMARD as biologic DMARD users, and those with a prescription for methotrexate (MTX) but no biologic DMARD as MTX users. We used time-varying propensity scores to adjust for the large number of possible confounders and stratified proportional hazards regression to estimate the effects of biologic DMARDs on cancer. The primary end points were hematologic malignancies (lymphoma, multiple myeloma, and leukemia) and common solid tumors (colorectal, lung, stomach, breast, prostate, uterine, ovarian, urinary tract/bladder, and melanoma).


RESULTS
The pooled cohort included 1,152 biologic DMARD users and 7,306 MTX users. We identified 11 hematologic malignancies and 46 solid tumors during 2,940 person-years of biologic DMARD use, and 88 hematologic malignancies and 558 solid tumors during 30,300 person-years of MTX use. Comparing biologic DMARD users with MTX users, the propensity score-adjusted pooled hazard ratio was 1.37 (95% confidence interval 0.71-2.65) for hematologic malignancies and 0.91 (95% confidence interval 0.65-1.26) for solid tumors.


CONCLUSIONS
Our results indicate that users of biologic agents are unlikely to have a substantial increase in the risk of hematologic malignancies and solid tumors as compared with MTX users. Despite the use of large combined data sets, studying the effect of an infrequent exposure (biologic DMARDs) on rare diseases (hematologic malignancies) remains a challenge.
Setoguchi
Soko
S
Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02130, USA. ssetoguchi@partners.org
Solomon
Daniel H
DH
Weinblatt
Michael E
ME
Katz
Jeffrey N
JN
Avorn
Jerry
J
Glynn
Robert J
RJ
Cook
E Francis
EF
Carney
Greg
G
Schneeweiss
Sebastian
S
D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000188:drug therapy; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012044:Regression Analysis; D018570:Risk Assessment; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha