OP0052 SWITCHING FROM IL-6R INHIBITORS TO OLOKIZUMAB, A DIRECT IL-6 INHIBITOR: EFFICACY AND SAFETY AT 1-YEAR FOLLOW-UP
Authors: E. Feist, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Olokizumab (OKZ) is an IL6 inhibitor that significantly reduces the symptoms of moderate to severe rheumatoid arthritis. Unlike tocilizumab or sarilumab, OKZ blocks the ligand, not the receptor. Currently, according to EULAR recommendations, intragroup switching to another iIL-6 is possible, if the first iIL-6 is ineffective. However, there is lack of information concerning effectiveness of switching from a receptor inhibitor to OKZ, as well as retention rate after such switching. The ability of OKZ to maintain remission achieved on receptor blockers is also of considerable interest. <h3>Objectives:</h3> To investigate the efficacy, safety, and retention on OKZ therapy over 12 months after switching from an IL-6 receptor inhibitor. This observation is continuing the study presented in 2023[1]. <h3>Methods:</h3> This retrospective cohort study included available efficacy and safety data of OKZ in patients with RA after switching from tocilizumab (IV or SC) or sarilumab (SC) from 11 of participating centers. Who achieved remission on previous therapy data were collected 2 and 1 month before switching to OKZ, and 1, 2, 6 and 12 months after switching. Efficacy assessments and routine biochemical data were analyzed using descriptive statistics – mean with standard deviation for continuous parameters and absolute and relative frequency for binary variables. AE were reported by participating centers according to patient's files. The statistical significance of data of the analyzed variable at a particular visit compared with previous visits or with the Switch visit was determined using paired t-test. Fisher's exact test or chi-square test was used to compare the proportion of patients with improvement/no change and worsening. All tests were 2-tailed, and a p-value &lt;0.050 was considered statistically significant. <h3>Results:</h3> We collected efficacy and safety results for 110 RA patients with a mean age of 47.8 (15.7) years, including 87 (79.1%) women. 77 (70.0%) patients were RF/ACPA positive. Mean RA duration was 13.1 (8.9) years and mean duration of treatment with an IL-6 receptor inhibitor was 47.8 (30.0) months. Mean interval before switching to OKZ was 54.7 (35.4) days with the main reason of unavailable IL6-R inhibitor. Patients were treated with OKZ 64mg q4w SC. The proportion of patients remaining on OKZ therapy was 97.3% within 6 months after switching, and 88.2% within 12 months. The percentage of patients who achieved remission/low activity after 6 and 12 months of therapy was 74.8% and 84.0% for DAS28-CRP, 70.5% and 81.0% for DAS28-ESR. Table 1. The changes of clinical indices were investigated in two groups –switched up to 40 days after the last iIL6-R administration (n=60) and more than 40 days after the last iIL-6R administration (n=50). Activity had not significantly change and had achieved 2.5(1/2)/2.2(0.9) DAS28-CRP and 2.4(1.2)/2.1(0.9) DAS28-ESR in the first group by the 6th and 12th month on therapy. In the second group activity had increased for DAS28-CRP 3.7(1.6) and for DAS28-ESR 3.6(1.7) by the time of switching, and reached the initial values by the 6th month of therapy, for DAS28-CRP 2.7(1.0) and for DAS28-ESR 2.7(1.1), and was significantly higher compared to the first group. Figure 1. Therapy was interrupted due to lack of effectiveness in 5 (4.5%) patients - 1 patient after 6 months of therapy, 4 patients from 6 to 12 months of therapy (3 patients were switched back to tocilizumab). Therapy was interrupted due to AEs in 2 patients, due to patient decision in 1 patient, due to non-medical reasons in 1 patient. No AEs of special interest were recorded over 12 months. Therapy was interrupted due to AEs in 2 patients, at the discretion of (1) patien in 1 patient, due to non-medical reasons in 1 patient. No AEs of special interest were recorded over 12 months. <h3>Conclusion:</h3> Remission was maintained in the majority of RA patients switched from an iIL6-R to OKZ for at least 12 months. Switching within the period, recommended by guidelines, prevents exacerbation of RA and maintains remission/low activity up to 1 year. There were no significant safety signals for OKZ during the 12-month treatment period. <h3>REFERENCES:</h3> [1] ARD 2023 V82, Sap 1, p.595, POS0639. <h3>Acknowledgements:</h3> Anoshenkova O., Antipova O., Baranov A., Bogdanova E., Grabovetskaya Y., Ilivanova E., Kalyagin A., Blinova A., Lapkina N., Mokrousova M., Nesmeyanova O., Nikitina N., Shesternya P., Vinogradova I., Yudina N. <h3>Disclosure of Interests:</h3> Eugen Feist Abbvie, BMS, Galapagos, Lilly, Novartis, Medac, Pfizer, R-Pharm, Evgeny Nasonov AbbVie, BMS, Novartis, Pfizer, R-Pharm.