AB0279 IMPACT OF DISEASE-MODIFYING DRUGS IN SECOND BIOLOGICAL TREATMENT SURVIVAL IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Briones-Figueroa, M. Tortosa-Cabañas, B. A. Blanco Cáceres, J. Bachiller-Corral, M. Vázquez Díaz
Journal: Annals of the Rheumatic Diseases (2020)

Background: Several studies have proposed that the immunosenescence of elderly patients with Rheumatoid Arthritis (RA) in treatment with biological therapies could eliminate the need for concomitant immunosuppression with disease-modifying drugs (DMARDs), due to a probable lower production of anti-drug antibodies; however, the evidence is limited. Objectives: To compare the characteristics of patients with RA who started a second biological agent, according to age groups. To analyse second biological agent survival and its relationship with DMARDs. Methods: Retrospective, observational and longitudinal study. Patients with RA who started a second biologic between 2000 and 2019, who discontinued a first-line TNF inhibitor, were included. Demographic, clinical and analytical data were obtained. The sample was divided in 2 groups: &lt;70 and ≥70 years old. A comparative analysis was performed. Kaplan-Meier curves and Log-rank were used to conduct the survival analysis. Results: 156 patients were included. 83.3% were women, with a mean age at the beginning of second biological treatment of 54.64±13.54 years. 22 patients (14.1%) were ≥70 years. Comparative analysis is detailed in table 1: patients ≥70 years presented a longer time from diagnosis to the start of biological treatment, and a higher prevalence of hypertension and diabetes mellitus. The main cause of withdrawal in this group was adverse events (46.67%) while in younger patients was treatment failure (25.27% primary failure, 29.66% secondary failure). The most frequent biological agent in ≥70 years was Rituximab (27.26%) while in &lt;70 years was Etanercept (26.12%). 126 patients (80.8%) had a DMARD associated. In both groups, Methotrexate was the most frequent (table 2). The second biological agent survival analysis showed that patients who received a DMARD presented a higher survival [77 months (55.50-98.55) vs. 51.53 months (41.67-61.40); p=0.023]. After conducting a survival analysis in patients whose withdrawal cause was treatment failure, DMARDs use was associated with an increased biological agent survival in patients &lt;70 years [103.48 months (82.28-124.68) vs. 81.95 months (66.05-97.86); p=0.037]; but statistical differences were not found in patients ≥70 years [117.33 months (82.15-152.52) vs. 65.07 months (40.72-89.42); p=0.291]. Table 1. Variable &lt;70 years = 134 (mean ± SD or %) ≥70 years = 22 (mean ± SD or %) p Age at diagnosis (years) 40.5 ± 12.3 58.8 ± 8.9 &lt;0.001 Age at the beginning of the treatment (years) 51.28 ± 11.44 75.14 ± 3.5 &lt;0.001 Time since diagnosis (years) 10.65 ± 8.20 16.27 ± 9.09 0.003 Women 113 (84.33%) 17 (77.27%) 0.373 Smokers 29 (21.64%) 2 (9.09%) 0.320 Rheumatoid factor positive 109 (81.34%) 17 (77.27%) 0.770 Anti-CCP positive 114 (90.48%) 14 (82.35%) 0.390 Erosions 92 (70.23%) 16 (76.19%) 0.576 Arterial hypertension 28 (21.37%) 14 (66.67%) &lt;0.001 Diabetes mellitus 3 (2.24%) 4 (18.18%) &lt;0.001 Retirement 91 (67.91%) 15 (68.18%) 0.980 Infections 10 (7.46%) 3 (13.64%) 0.397 Second biological agent withdrawal cause Primary failure 23 (25.27%) 3 (20%) 0.242 Secondary failure 27 (29.66%) 3 (20%) Adverse events 25 (27.47%) 7 (46.67%) Remission 2 (2.20%) 0 (0%) Exitus 3 (3.30%) 0 (0%) Neoplasia 3 (3.30%) 0 (0%) Table 2. Disease-modifying drug &lt;70 years old ≥70 years old p Methotrexate 72 (53.73%) 9 (40.91%) 0.667 Leflunomide 22 (16.42%) 5 (22.73%) Sulfasalazine 2 (1.49%) 1 (4.55%) Hydroxychloroquine 6 (4.48%) 0 (0%) At least two of the above 7 (5.22%) 1 (4.55%) Conclusion: DMARD concomitant treatment has been related to a higher second biological treatment survival. This beneficial effect was not observed in RA patients ≥70 years of age whose second biological agent withdrawal cause was failure. In this age group, withdrawal related to adverse events was more frequent. References: [1]Kalden JR, Schulze-Koops H. Immunogenicity and loss of response to TNF inhibitors: implications for rheumatoid arthritis treatment. Nature reviews Rheumatology. 2017;13(12):707-718. Disclosure of Interests: None declared