OBJECTIVES: Targeted drugs against key pathogenetic molecules such as TNF-alpha 
have significantly improved outcomes in rheumatoid arthritis (RA). They are 
widely used in clinical practice and drug registries give us information to 
support their use. Adalimumab (ADA) is able to induce a comprehensive disease 
control in RA by achieving clinical, functional and radiographic control.
METHODS: By interrogating 2 Italian registries, LORHEN and GISEA, we analysed 
the efficacy of ADA in first- or second-line in a total of 2262 RA patients.
RESULTS: Patients in 1st line were significantly older, with lower disease 
activity and HAQ scores compared to 2nd line. In 1st line, rates of 
DAS28-remission (DAS28rem) at 2 years were 34.4% while 26.5% in 2nd line 
(p=0.038). A normal HAQ score (HAQ≤0.5) was achieved in 53.5% after 2 years in 
1st line versus 30.1% in 2nd (p<0.0001). DAS28rem+HAQ≤0.5, a combined parameter 
that we defined global clinical disease control, was reached in 20.7% in 1st 
line versus 13.3% in 2nd (p<0.01). Five-year-survival on therapy was higher for 
patients in 1st line (45.6% vs. 33.2%, p<0.0001). Discontinuation due to lack of 
efficacy was lower in 1st line (37.4 vs. 54.4%, p<0.0001). Rates of adverse 
events were similar.
CONCLUSIONS: Responses in 1st line are generally significantly better than after 
a first anti-TNF-alpha failure but patients in 2nd line have a worse clinical 
and functional profile. A global disease control with clinical and functional 
remission is an achievable target in both lines.