Background/Purpose: There is currently no consensus on selecting a therapeutic target in patients (pts) non-responsive to their first TNF inhibitors (TNFi). The development of anti-drug antibodies (ADA) is a frequent cause of secondary inefficacy in our pts with TNFi and there is evidence that those who develop ADA at their 1st TNFi 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 TNFi. The objective of this study was to assess if development of ADA to the 1st TNFi determines better response when switching to a 2nd TNFi versus a nonTNFi. As secondary objective, it was analyzed whether the presence or absence of ADA to a 1st TNFi influences the efficacy of a 2nd TNFi

Methods: Of a total of 110 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 TNFi, 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. T tests and Fisher’s exact test were used to test statistical differences. Analysis was performed using SPSS version 20.0

Results: Within the 60 pts who had measured DL/ADA at suspension of the 1st TNFi, 26 (43%) were ADA-. In this ADA- subpopulation, 50% changed to a 2nd TNFi; at v-6 there were no differences between switchers to a 2nd TNFi and switchers to a nonTNFi in DAS28 (3.7±2.1 TNFi vs 4.2±1.1 nonTNFi, p=0.286), ΔDAS28 (1,4±2 TNFi, 1±1,2 nonTNFi, p=0,374) and resp-E (75% good/moderate resp in TNFi, 40% in nonTNFi, p=0,064). At v-12, switchers to a 2nd TNFi showed a lower DAS28 (2.5±0.6 TNF-i, 3.9±0.9 nonTNFi, p=0.009) and a higher good E-resp rate with a marginally significant difference (80% in TNFi, 22% in nonTNFi, p=0.071). However, at v-end, pts with a 2nd nonTNFi had better response (DAS28 > 5,1 in 50% of TNFi pts, 0% of nonTNFi, p=0.044). Likewise ΔDAS28 at v-end was higher in the nonTNFi group (0,7±1,7 TNFi, 1,7±0,8 nonTNFi, p=0,06). Along these lines, the good/moderate E-resp rate was higher in switchers to a nonTNFi (30% in TNFi, 92% in nonTNFi, p=0.006). In ADA+ subpopulation (n=34), no differences were found at v-end in DAS28 (3.7 ± 1.2 TNF-i, 3.9±1.1 nonTNFi, p=0.64), ΔDAS28 (0,63±1,6 in TNFi, 1,4±1,4 in nonTNFi, p=0,35) and good/moderate E-resp rate (65% in TNFi, 75% in nonTNFi, p=0,703). In pts who changed to a 2nd TNFi, those with ADA to 1st TNFi had a higher good response rate than ADA- pts (65% in ADA +, 30% in ADA-, p=0.07).

Conclusion: The development of ADA to the first TNFi entails a better response when switching to a 2nd TNFi, with a similar efficacy to the pts who switched to a nonTNFi. In those pts who did not develop immunogenicity to the 1st TNFi, there is a better response when changing therapeutic target. The ADA measurement can help to select the pts who can benefit from a 2nd TNFi.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/influence-of-immunogenicity-to-the-first-anti-tnf-therapy-on-response-to-the-second-biologic-agent-in-ra-patients/