Impact of the change in administration route of tocilizumab and abatacept, due to the COVID-19 lockdown on disease activity in patients with rheumatoid arthritis

ABSTRACT

Background: Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration. Objectives: The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient's request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown. Methods: We conducted a prospective monocentric observational study. Eligibility criteria Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6) demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci & Gagnon, HAD). The primary outcome was the proportion of patients with a DAS28 variation≥1.2 at M6. Analyses Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis. Results: Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics female 81%, mean age 62.7, mean disease duration 16.0, ACPA positive 72.4%, mean DAS28 2.01, previously treated with SC TCZ or ABA 17%. At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening≥1.2 (ABA 5/17 [29.4%] and TCZ 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening≥0.6 (ABA 11/17 [64.7%] and TCZ 8/32 [25.0%], p= 0.007). At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening≥1.2 and≥0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively. Conclusion: The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.