BACKGROUND: Anti-tumour necrosis factor-alpha (TNF-alpha) therapies represent an 
important advancement in therapy for rheumatoid arthritis (RA). However, there 
remains a proportion of patients who do not improve despite therapy. These drugs 
are expensive and have the potential of serious toxicity. Therefore, it would be 
ideal to predict the patients who will respond, so that the use of these drugs 
can be targetted.
OBJECTIVE: To identify the clinical factors present at the start of 
anti-TNF-alpha therapy that are associated with response at 6 months in patients 
with RA.
METHODS: The British Society for Rheumatology (BSR) Biologics Register collects 
detailed data on all patients with a rheumatic disease receiving biologic 
therapy in the UK. We studied all patients with RA who had started etanercept 
(ETA) or infliximab (INF) and had achieved a minimum 6 months follow-up by 1 
October, 2004. The disease status at the baseline and at 6 months was assessed 
using the Disease Activity Score (DAS28). The response was classified according 
to the European League against Rheumatism (EULAR) improvement criteria. The 
effect of baseline characteristics on response was studied using multivariate 
ordinal logistic regression.
RESULTS: 2879 patients were included in this analysis (1267 ETA, 1612 INF). At 
the start of therapy, the mean age was 55 yrs, disease duration 14 yrs, baseline 
DAS28 6.7 and health assessment questionnaire (HAQ) 2.1. In all, 28% of ETA and 
86% of INF patients were receiving methotrexate. After 6 months, 18% had a good 
EULAR response, of whom 9% were considered to be in remission and 50% had a 
moderate response. There was no overall difference in response rate between the 
two anti-TNF-alpha therapies. A higher baseline HAQ score correlated with a 
lower response rate while a better response was associated with the current use 
of NSAIDs and the use of methotrexate (MTX), although the latter only reached 
statistical significance with ETA [OR 1.82 (95% CI 1.38-2.40)]. There was a 
lower response rate among current smokers, particularly in patients receiving 
INF [OR 0.77 (95% CI 0.60-0.99)]. Age, disease duration, rheumatoid factor and 
the previous number of disease-modifying antirheumatic drugs (DMARDs) did not 
predict response to either drug. However, females were less likely to achieve 
remission.
CONCLUSIONS: These data support an improved outcome among patients receiving MTX 
in combination with anti-TNF-alpha therapies. However, the most disabled 
patients were less likely to respond, despite concurrent MTX. The benefits of 
NSAIDs may reflect the relative absence of comorbidities in patients who can 
tolerate these drugs or the continuing presence of reversible inflammatory 
symptoms. The association of smoking and poor outcome with INF is a novel 
finding and may reflect alterations in pharmacokinetics. The inability of other 
baseline disease characteristics to predict the outcome suggests that other 
factors, including potential genetic differences in drug metabolism, may be 
influencing the response to anti-TNF-alpha therapies.