FRI0186 Influence of immunogenicity to the first tnf-i therapy on response to the second biologic agent in ra patients. (15th June 2017)

• Record Type: Journal Article
• Authors: Bogas, P; Plasencia, C; Pascual-Salcedo, D; Bonilla, G; Moral, E; Tornero, C; Nuño, L; Villalba, A; Peiteado, D; Martinez, A; Hernandez, B; Balsa, A
• Is Part Of: Annals of the rheumatic diseases. Volume 76(2017)Supplement 2
• Page Start: 551
• Page End: 552
• Publication Date: 2017-06-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-eular.6688
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: There is currently no consensus on selecting a therapeutic target in patients (pts) non-responsive to their first TNF-inhibitors (TNF-i). The development of anti-drug antibodies (ADA) is a frequent cause of secondary inefficacy in our pts with TNF-i and there is evidence that those who develop ADA at their 1st TNF-i achieve a higher degree of response to the second one, compared to ADA- pts. Thus ADA measurement can help in choosing a therapeutic target in pts who failed to respond to their 1st TNF-i Objectives: To assess if development of ADA to the 1st TNF-i determines better response when switching to a 2nd TNF-i versus a nonTNF-i. As secondary objective, analyze whether the presence or absence of ADA to a 1st TNF-i influences the efficacy of a 2nd TNF-i Methods: Of a total of 144 pts that switched from infliximab or Adalimumab to a 2nd biologic agent (Etanercept, Rituximab, Tocilizumab, Adalimumab, Abatacept, Certolizumab and Infliximab), only 60, who had measured drug levels (DL)/ADA at discontinuation of the 1st TNF-I, were included. Clinical response was evaluated with DAS28, Delta-DAS28 (ΔDAS28) and EULAR response (E-resp) at 6 (v-6) and 12 (v-12) months after initiating 2nd biologic agent and at the last visit prior to drug discontinuation or ending of the study for those who did not interrupt the biological therapy (v-end). DL/ADA levels were measured by ELISA. Statistical analysis was performed using SPSS version 20.0 Results: Within the 60 pts who had measured DL/ADA at suspension of the 1st TNF-i, 26 (43%) were ADA- (i.e. DL +). In this ADA- subpopulation, 50% changed to a 2nd TNF-i; at v-6 there were no differences between switchers to a 2nd TNF-i and switchers to a nonTNF-i in DAS28 (3.7±2.1 TNF-i vs 4.2±1.1 nonTNF-i, p=0.286), ΔDAS28 (1, 4±2 TNF-i, 1±1, 2 nonTNF-i, p=0, 374) and resp-E (75% good/moderate resp in TNF-I, 40% in nonTNF-i, p=0, 064). At v-12, switchers to a 2nd TNF-i showed a lower DAS28 (2.5±0.6 TNF-i, 3.9±0.9 nonTNF-i, p=0.009) and a higher good E-resp rate with a marginally significant difference (80% in TNF-i, 22% in nonTNF-i, p=0.071). However, at v-end, pts with a 2nd nonTNF-i had better response (DAS28 >5, 1 in 50% of TNF-i pts, 0% of nonTNF-i, p=0.044). Likewise ΔDAS28 at v-end was higher in the nonTNF-i group with trend to significance (0, 7±1, 7 TNF-i, 1, 7±0, 8 nonTNF-i, p=0, 06). Along these lines, the good/moderate E-resp rate was higher in switchers to a nonTNF-i (70% in TNF-i, 8.3% in nonTNF-i, p=0.006). In ADA+ subpopulation (n=34), no differences were found in clinical response at v-end in DAS28 (3.7±1.2 TNF-i, 3.9±1.1 non-TNF-i, p=0.64), ΔDAS28 (0, 63±1, 6 in TNF-i, 1, 4±1, 4 in nonTNF-i, p=0, 35) and good/moderate E-resp rate (30% in TNF-i, 91% in nonTNF-i, p=0, 703). In pts who changed to a 2nd TNF-i, those with ADA to 1st TNF-i had a higher good response rate than ADA- pts (65% in ADA +, 30% in ADA-, p=0.07) Conclusions: The development of ADA to the first TNF-i entails a better response when switching to a 2nd TNF-i, with a similar efficacy to the pts who switched to a nonTNF-i. In those pts who did not develop immunogenicity to the 1st TNF-I, there is a better response when changing therapeutic target. The ADA measurement can help to select the pts who can benefit from a 2nd TNF-i Disclosure of Interest: None declared