There were 16 tumors (including five lymphomas) in 1603 person-years at risk in those who received biologic therapy, while the control group sustained 69 tumors (including two lymphomas) in 3948 person-years. The standardized incidence ratios (SIR) for total tumor relative risk for the anti-TNF group and the comparison group were 1.1 and 1.4, respectively. The lymphoma relative risk (RR) was 11.5 and 1.3, respectively, and the total tumor RR excluding lymphoma was 0.79 for those receiving anti-TNF therapy and 1.39 among those treated with conventional DMARDs.
Specifically, the types of lymphomas diagnosed in this cohort, including non-Hodgkin's lymphoma and Hodgkin's disease, seem to "be well in line with those recently reported in RA patients, possibly suggesting that these are more related to diagnosis than treatment," note researchers at Lund University Hospital in Lund, Sweden. "This requires further study of a larger sample of lymphomas in RA patients treated with TNF inhibitors."
The research team, led by Pierre Geborek, MD, PhD, rheumatologist at Lund University Hospital, note that the "relatively short time interval between the initiation of anti-TNF treatment and lymphoma diagnosis in the current report might suggest both an increased awareness of such a possible relationship and more careful surveillance."
The new study utilized the South Swedish Arthritis Treatment Group registry, which comprises more than 90% of the anti-TNF treated RA patients in the catchment area. Researchers compared 757 RA patients treated with etanercept (EnbrelR) or infliximab (RemicadeR) between February 1, 1999, and December 31, 2002, with 800 control patients who were administered conventional DMARDs. Patients were followed from initiation of TNF-blockade or July 1, 1997, for the controls until death or December 31, 2002. Researchers identified tumors and deaths in the cancer registry and population census registers.
Relationship Between TNF Blockade and Lymphoma
"To state that we have the final proof of anti-TNFs and lymphoma association would be somewhat presumptuous, to say the least," Dr. Geborek tells CIAOMed. "We prefer to put it the more European (and Scandinavian) way – this is one piece [that] will in the future give a more comprehensive picture and add to the bulk of information."
Anecdotal reports and recent hearings by the US Food and Drug Administration have pointed to a possible increase in the rate of lymphomas/leukemias in patients taking anti-TNF drugs.2
Salahuddin Kazi, MBBS, chief of the section of rheumatology at the Dallas VA Medical Center in Dallas, Texas, tells CIAOMed that "this article again confirms what we have suspected about TNF therapy and RA and the increased risk of lymphoma in patients on anti-TNF therapy."
However, he points out, "this is not a controlled study and there is the issue of confounding by indication which means that patients with more severe RA are more likely to be treated with anti-TNF therapy and, because patients with more severe RA are at higher risk for lymphoma, the severe RA, and not the therapy, may be the real reason for the increased risk of lymphoma in this group."
References:
1. Geborek P, Bladstrom A, Turesson C, et al. TNF blockers do not increase overall tumor risk in patients with rheumatoid arthritis, but may be associated with increased risk of lymphomas. Ann Rheum Dis. 2005 Feb 4; [Epub ahead of print].
2. Brown SL, Greene MH, Gershon, SK, Edwards ET, Braun MM. Tumour necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration. Arthritis Rheum. 2002;46:3151-3158.