Abstract 727: Response to Second or Third TNF Inhibitor in Rheumatoid Arthritis: Results from an Observational Study
Authors:
J. Karlsson, L. Kristensen, M. C. Kapetanovic, A. Gülfe, T. Saxne, P. Geborek
Background
As more non-TNF inhibitor biologics are introduced, many practitioners are wondering whether there is clinical utility in switching to alternative TNF inhibitors in RA patients who have failed a first TNF inhibitor, or whether TNF inhibitor therapy should be abandoned after failure of one representative of the class. This clinical dilemma was addressed using data from the South Swedish Arthritis Treatment Group (SSATG).
Methods
Subjects enrolled in the SSATG register with at least 12 weeks of follow-up who had switched to their second or third TNF inhibitor between March 1999 and December 2006 were studied. EULAR and ACR responses after switching were assessed at 12 weeks. Demographic and disease characteristics were evaluated as predictors of response.
Results
There were 337 first-time switches and 36 second-time switches. The mean age of first-time switchers was 56 vs. 58 for second-time switchers. Mean DAS28 score at the time of switching was 5.5 for first-time switchers and 5.8 for second time switchers. At 12 weeks 51%, 21%, and 7% of first time switchers had achieved an ACR 20, 50, and 70 response, respectively compared to 35%, 18%, and 3% of second-time switchers. First-time switchers achieved a EULAR good response 25% of the time vs. 9% in second time switchers. EULAR remission was achieved in 16% of first time switchers vs. 6% of second-time switchers. Univariate predictors of response to switching included lower age, lower baseline HAQ, higher baseline DAS, and prior discontinuation for adverse events (as opposed to inefficacy). No single predictor was significantly associated with all response outcomes.
Conclusions
Response rates after second-time TNF inhibitor switches are lower than those of first-time switches, suggesting that alternate therapies should be tried after failure of the second TNF inhibitor.
Editorial Comment
These findings are supportive of a recent report of participants in the British Society for Rheumatology Biologics Register that demonstrated high rates of continuation for the second TNF-inhibitor after failure of the first. In contrast to the abstract presented here, that report showed higher continuation rates in patients with prior inefficacy compared to prior adverse events. Regardless, the message appears fairly clear that a second TNF-inhibitor should be tried after failure of a first, if use has not become contraindicated. Even so, the question of whether a non-TNF inhibitor biologic is superior to a second TNF inhibitor remains to be directly studied. Although the number of patients in this investigation who switched to their third TNF inhibitor is a little low to firmly draw conclusions about response, there is a suggestion that response rates are lower and, unless other options are not available, the third TNF inhibitor may not be an appropriate option for patients unfortunate enough to fail two other TNF blockers.
