Background/Purpose: Tumour necrosis factor inhibitors (TNFi) are highly effective treatments for active Rheumatoid Arthritis (RA). However, up to 40% of patients either fail to respond adequately to TNFi or lose response over time. Options available include treatment with a 2^nd TNFi or switching to a biological therapy with a different target such as Tocilizumab (TCZ) or Rituximab (RTX).

Objectives: To compare the effectiveness of a 2^nd TNFi, TCZ or RTX, measured by stratified persistency rates, in RA patients with previous discontinuation of their 1^st TNFi; to compare the response rates of TNFi, TCZ or RTX at 6 months, 1 and 2 years; to clarify the frequency and reasons for treatment discontinuation.

Methods: Non-interventional prospective study of RA patients exposed to a 2^nd TNFi, TCZ or RTX treatment after previous TNFi discontinuation using real-world data from the Reuma.pt database. Patient and disease baseline characteristics, disease activity at follow-up (6 and 12 months and every year thereafter), discontinuation date and reason were collected and compared according to biologic class. Persistency of RTX, TCZ and TNFi were estimated using Kaplan-Meier analysis, from initiation of each therapy until discontinuation/ switch or last follow-up visit.

Results: 643 patients were included, 88.8% females, with a mean age of 59.4 (±12.8) years. After 1^st TNFi discontinuation, 390 (60.7%) patients initiated a 2^nd TNFi, 147 (22.9%) TCZ and 106 (16.5%) RTX. There were no significant differences in patient and disease characteristics among the 3 groups, except for extra-articular manifestations, higher in RTX group (p=0.013), education (p=0.002) and current full-time employment (p<0.001), both lower in RTX patients. At baseline, TNFi group included more patients treated with concomitant methotrexate (p=0.002) and a higher swollen joint count-28 (p=0.010). However, the disease activity according to DAS28, CDAI and SDAI were similar between the different therapy groups. The persistency rates according to Kaplan-Meier survival curve were significantly greater (log rank test, p<0.001) among patients who initiated TCZ or RTX. The multivariate analysis showed a lower risk of discontinuation for TCZ (HR 0.39, 95% CI 0.23-0.64, p<0.001) and RTX (HR 0.42, 95% CI 0.25-0.72, p=0.001) and a significant risk for discontinuation for smoking (HR 2.43, 95% CI 1.50-3.95, p<0.001) and higher HAQ at baseline (HR 1.51, 95% CI 1.14-2.00, p=0.004), adjusted for gender, disease duration and comorbidities. The proportion of patients with a EULAR good response at 6 months (p<0.001), 1 (p<0.001) and 2 years (p=0.021) were, respectively, 23.7%, 28.0%, 31.4% for TNFi, 51.7%, 54.4%, 55.9% for TCZ and 27.5%, 23.1%, 25.6% for RTX. The main reason for discontinuation was inefficacy for TNFi and RTX and adverse events for TCZ (p<0.001).

Conclusion: Our findings showed a significantly higher drug persistence for RTX and TCZ compared with 2^nd TNFi and a similar persistence among RTX and TCZ, in patients with previous TNFi discontinuation. These data corroborate the notion that switching to a biologic with a different mechanism of action might be more effective after TNFi discontinuation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-long-term-effectiveness-of-switching-to-another-tumour-necrosis-factor-antagonists-tocilizumab-or-rituximab-in-patients-with-rheumatoid-arthritis-and-inadequate-response-to-a-first-line-t/