Background The use of biological DMARDs to treat RA patients has increased over the past 15 years probably due to their efficacy and tolerability profile.
Objectives Describe persistence (time between biological agent initiation and its discontinuation), the impact of biological therapy (BT) in clinical outcomes (DAS28) and the reasons for its discontinuation.
Methods A retrospective study of RA patients (pts) followed at Hospital Garcia de Orta with 1st BT [abatacept (ABT), adalimumab (ADA), anakinra (ANA), etanercept (ETN), golimumab (GLM), infliximab (IFX), rituximab (RTX), and tocilizumab (TCZ)] starting between 1/1/2001 and 31/7/2014. Electronic clinical records (Reuma.pt database) were reviewed for all pts that have been treated at least 12 months previously to their recruitment. Available demographic, clinical and therapeutic data were collected. Survival methods were used to analyze time to an event.
Results 97 RA pts with mean age at RA diagnosis of 45.4±13.4 years were included. 86% were women, 53% with erosive disease, 66% with positivity for rheumatoid factor and 70% with positivity for anti-CCP antibodies. The mean age at the beginning of BT was 53.0±12.7y. Concerning 1st BT, ETN was the most frequent one (36%), followed by IFX (30%), and ADA (27%). 61 pts discontinued their 1st BT, mainly due to secondary ineffectiveness (15 IFX, 10 ETN, 9 ADA, 2 ANA and 1 TCZ). The median time on 1st line was 59.6 months (plot 1). The treatment persistence was not significantly different between BT (p=0.6). Notwithstanding, ETN showed a higher median persistence (96.1 months) than the others (plot 2). Comparing with IFX, the adjusted risk of discontinuation was 42% and 33% inferior with ETN and ADA respectively, though statistical significance was not reached. More than 50% of pts discontinued 1st BT within first 5 years. 46 pts started a 2nd BT (19 ETN, 13 ADA, 5 IFX, 5 RTX and 4 others). Of these, 21 discontinued most due to secondary ineffectiveness (7 ADA, 3 IFX and 3 ETN). The median time on 2nd line was 43.2 months (plot 3). The differences between BT in persistence are fairly statistically significant (p=0.06). Again, ETN showed a higher median persistence (43.5 months) followed by ADA (11.5 months) (plot 4). ADA as 2nd BT presented an adjusted risk to discontinue almost 4 times higher than ETN (HR=3.98, p=0.02). 15 pts switched their 2nd BT (5 TCZ, 4 ABT, 4 RTX e 2 ETN). More than 50% of the pts discontinued their 2nd BT within 4 years after starting it. The adjusted risk for switching with ADA was 9 times higher than the risk for switching ETN (HR=9.06, p=0.004). Regarding evolution of DAS28 during 1st line, ETN presented the highest variation from the baseline at 3, 6, 12, 18 and 30 months compared with all other agents. Regarding 2nd BT, the longitudinal analysis revealed that all agents achieved response between 6 and 18 months after treatment initiation.
Conclusions The analysis per BT suggests that ETN was the TNF antagonist with the highest persistence on treatment and efficacy profile. Comparing 1st and 2nd lines of biological therapy, there is a decrease of 16.4 months on persistence. Additionally, the probability of switch increases and the probability of end of treatment decreases from 1st to 2nd line.
Disclosure of Interest None declared