Background The induction of auto-antibodies, such as anti-nuclear antibodies (ANA), is a well-known phenomenon during anti-TNF alpha treatment. However, the correlation of this increase in ANA production and clinical response to anti-TNFα in Rheumatoid Arthritis (RA) patients is not yet determined.
Objectives To evaluate the increase in ANA production during anti-TNFα treatment and its impact in clinical response and persistency of anti-TNFα inhibitor in RA patients.
Methods Observational retrospective cohort study was performed. Patients fulfilling American College of Rheumatology criteria for RA, who started their first anti-TNFα between 2002 and 2013, and had performed serial ANA testing (titter >1/100), were included. Disease activity (assessed by DAS28) was measure at baseline, 6, 12, 18 and 24 months (M). Clinical response was evaluated by EULAR criteria and three categories of response were defined: good, mild and no response. Demographic, clinical and laboratory data were obtained by consulting the clinical process and Rheumatic Diseases Portuguese Register Reuma.pt. Statistical analyses were performed using t-test, Mann-Whitney U-test, Chi-square and McNemar test. Kaplan-Meier survival analysis (time for evaluating drug survival defined as time between starting anti-TNFα and their discontinuation) was used to assess persistence, log rank tests were used to compare drug survival. (SPSS 21.0)
Results 74 patients were included. 90% (65) were female with a mean age of 54.56 years (SD ± 10.57). The median follow-up time for this cohort was 2.88 years [1-11.09]. At baseline, ANA were positive in 27.4% (20) patients. We found a seroconversion rate for ANA of 33.8% (n=25) with median time of 18 months [0-91.4]. Infliximab group demonstrated higher ANA seroconversion rate (60%, 3/5) compared with adalimumab (48% 15/31), etanercept (17.2%, 5/29) and golimumab (22.2% 2/9) (p=0,035).
No statistically significant differences were found in Das28, DAS28 changes and EULAR response at 6, 12, 18 and 24M, between patients with ANA seroconversion versus absence of seroconversion. However, patients with ANA seroconversion had higher switch rate (56%, 14/25 versus 22.4%, 11/49, p=0.05). No differences were found in anti-TNF inhibitor discontinuation cause (adverse event or inefficacy) between the two groups. Survival of first anti-TNFα inhibitor was lower in patients with ANA seronversion (44%) than in patients without seroconversion (77.6%) and separation of survival curves had statistically significance (log-rank 6.025, p=0.014).
Conclusions We found a meaningful ANA seroconversion rate in RA patients after anti-TNFα treatment. Our study failed in demonstrates differences in activity and clinical response to anti-TNF inhibitor BETWEEN patients that had ANA seroconversion versus patients that had not. This may be explained by the small number of patients under infliximab. However our study suggests a higher switch rate in these patients, maybe because of the presence of late secondary inefficacy.
Disclosure of Interest None declared