Background Biological therapies have improved the treatment of Rheumatoid Arthritis (RA) in the last decade. The development of anti-TNF antibodies has been found crucial to drug efficacy and survival. All monoclonal antibodies are immunogenic, whereas the fusion proteins, like Etanercept, have proved to be less immunogenic in several studies.
Objectives To assess the survival of 3 anti-TNF agents in a cohort of patients with RA, and to determine if there are differences in the survival of the 3 anti-TNF between patients who develop or not immunogenicity.
Methods RA patients, who started Adalimumab (ADA), Infliximab (IFX) or Etanercept (ETN) as first biological treatment in a single center between 2002 to 2010 were included. Clinical and demographic data were collected: sex, age, rheumatoid factor, anti-CCP, disease duration, DMARD co-treatment, DAS28 at baseline, date of start and end of treatment and in the case of ADA and IFX, presence or absence of anti-drug antibodies. No patient with anti-ETN antibodies were identified. The reasons for drug discontinuation were classified as adverse event, administration reaction, inefficacy, remission and other (this included pregnancy, malignancies, lost of follow up, etc). The event was defined as drug discontinuation due to only the first 4 reasons. Cumulative incidence through competitive risk was performed to compare drug survival.
Results We studied 177 patients with a mean age of 54,7±14,2 years, 83,1% were women. Out of them, 39% (69) started treatment with IFX, 40,7% (72) with ADA, and 20,3% (36) with ETN. The lowest survival was of IFX with a probability of drug discontinuation of 28,1% at 500 days, and 61,4% at 2000 days (about 5 years), compared to 10,2% at 500 days and 35,5% at 5 years of ADA, and versus 14% at 500 days and 31,5% at 5 years of ETN, which was statistically significant (p=0,0001). Inefficacy was the most common reason for discontinuing IFX and ADA with 32,7% and 31,6% respectively, while 41,2% of patients treated with ETN discontinued treatment for reasons that mainly encompassed pregnancy, malignancies, etc.
Of the 69 patients treated with IFX, 43,3% developed anti-IFX antibodies (AIA). Anti-ADA antibodies (AAA) were observed in 15,2% of 72 patients who received ADA. In both drugs was found that drug survival was lower in the presence of anti-drug antibodies, as shown in the following table:
When survival was analyzed by subgroups of patients treated with IFX and ADA who had not developed antibodies compared with ETN, IFX still showed the lowest survival (probability of drug discontinuation at 5 years of 47,6%, versus 11,4% of ADA and 31,5% of ETN, p=0,003).
Conclusions In our cohort, IFX has proven to be the anti-TNF with the lowest survival, even in patients who do not develop immunogenicity. The survival of ADA was slightly higher than ETN only in patients who did not develop AAA. The development of anti-drug antibodies is a very important factor in the survival of anti-TNF treatment.
Disclosure of Interest None declared