Objectives: To systematically review and meta-analyse evidence on the effectiveness of the TNF-a
inhibitors when used sequentially.
Methods: Systematic review of comparative and single-arm observational studies. Data were synthesized
using random-effects meta-analysis. Treatment effects were estimated using four outcome measures from
the included studies: European League Against Rheumatism (EULAR) and ACR20 response rates and
mean improvement in disease activity score-28 (DAS-20) and HAQ. The effect of other factors was
explored via meta-regression and sub-group analyses.
Results: Twenty studies comprising 2705 patients were included in the analysis. All studies were observational
and most had no control group. Therefore, our primary analysis considered patient changes from
baseline. The mean percentage of ACR20 responders was 60.8% (95% CI 53.8, 67.4), EULAR responders
70.5% (95% CI 63.7, 76.6), mean overall improvement in DAS-28 scores was 1.53 (95% CI 1.25, 1.80) and
in HAQ scores was 0.25 (95% CI 0.11, 0.40). Four studies made comparisons with patients who received
TNF-a inhibitors for the first time. Response rates associated with sequential TNF-a inhibitor treatment
were lower than for first-time use.
Conclusions: Sequential TNF-a inhibitor use is likely to lead to treatment benefit in terms of the signs and
symptoms of disease and physical function. There is also some evidence to suggest that the probability of
achieving a response is lower, and the average magnitude of response is lower than the first use. Further
evidence from randomized controlled trials is required to confirm and further quantify the role specific
anti-TNF-a agents have when used sequentially.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)