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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