Background/Purpose: There are many biological therapies for Rheumatoid Arthritis (RA) with different mechanisms of action and good efficacy rate; however, up to 40% of patients (pts) fail to respond to the 1st biologic agent, and it is still not clear what strategy to follow after showing inadequate response to tumor necrosis factor α inhibitors (TNFi). Our objective was to assess the clinical response and survival (SVV), in our cohort of RA pts that discontinued the 1st TNFi, of a 2nd TNFi vs a nonTNFi, both in the global cohort and in the subpopulation that dropped out the 1st TNFi due to inefficacy

Methods: This observational study included 149 pts in the RA-Paz cohort who previously suspended Infliximab, Adalimumab, Etanercept and Certolizumab between 1999-2016. Two groups were established as they switched to a TNFi or nonTNFi. Clinical response was evaluated by DAS28, Delta-DAS28 (ΔDAS28) and EULAR response (E-resp). The assessments were performed at 6 (v-6) and 12 months (v-12) since initiating 2nd biological agent and during the last visit prior to drug discontinuation or ending of the study for those who did not interrupt the drug (v-end). T tests and Fisher’s exact test were used to test statistical differences. Analysis was performed using SPSS 20.0

Results: Of the 149 pts who had stopped their 1st TNFi, 61% changed to a 2nd TNFi. The 81% of the overall pts were women. The mean age was 62±14 years and the mean time of 2nd biologic drug was 3.03±3.2 years. 58% associated methotrexate at the beginning of 2nd biologic agent, without differences between groups. At v-6 and v-12, there was no difference in ΔDAS28 [at v-6:1.3±1.4 in TNFi and 1.2±1.2 in nonTNFi (p=0.95), at v-12: 1.3±1.4 in TNFi and 1.4± 1.1 in nonTNFi (p=0.88)]. In contrast, at v-end, pts with nonTNFi showed a higher clinical improvement (ΔDAS28: 0.8±1.7 in TNF-i, 1.7±1.2 in nonTNFi, p= 0.001). At v-6, the TNFi group achieved higher good E-resp rate (39% vs 18%, p=0.01), but there was no difference at v-12 (34% in TNF-I vs 23% in nonTNFi, p=0.42). However, at v-end, the nonTNFi group achieved better E-resp (good resp: 37% in nonTNFi vs 26% in TNFi, no resp 18% in nonTNFi vs 50% in TNFi, p=0.005). Likewise, 100% (n=9) of the pts that finished 2nd biologic agent by remission, had changed to a nonTNFi (p<0.00001). There were no differences regarding 2nd biologic drug SVV (mean SVV time of 5.2±0.6 in TNFi, 4.4±0.5 in nonTNFi, p=0.507). A multivariate analysis adjusted for possible confounding factors (sex, age, smoking, RF, anti-CCP and basal DAS28 and DMARDs) was performed; same behavior as in the main analysis was observed. When analyzing the cohort that discontinued 1st TNFi because of inefficacy, at v-6 and v-12 there were no differences between switchers to TNFi and nonTNFi in ΔDAS28 (p=0.192), but at v-end, the nonTNFi group reached a higher ΔDAS28 (0.9±1.5 in TNFi, 1.7 ± 1 in nonTNFi, p=0.031)

Conclusion: In our sample of RA patients who suspended Ifx/Ada/Etn/Ctz as 1st TNFi, switching to a 2nd biologic agent did not show relevant clinical differences between a TNFi and a nonTNFi within the 1st year of treatment. However, in the long-term, switching to a nonTNFi shows enhanced clinical benefits with no impact on survival vis-à-vis a 2nd TNFi. Despite the efficacy of TNFi, new therapeutic targets are needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-the-long-term-clinical-outcomes-between-non-anti-tnf-versus-anti-tnf-in-ra-patients-who-failed-to-a-first-anti-tnf/