AB0324 REASONS FOR DISCONTINUATION OF BIOLOGICS IN PATIENTS WITH REFRACTORY RHEUMATOID ARTHRITIS: RESULTS OF A RETROSPECTIVE STUDY
Authors: V. Sygyrta, S. Glukhova, E. Aronova, A. Satybaldyev, A. Lila
Journal: Annals of the Rheumatic Diseases (2020)

Background: Refractory rheumatoid arthritis (RRA) is a subtype of rheumatoid arthritis (RA), in which the sequential administration of optimal methotrexate (MT) doses in combination with glucocorticoids (GCs), and at least - two biologic disease-modifying antirheumatic drugs (bDMARDs) with different mechanisms of action during 18-24 months does not lead to a significant decrease in the inflammatory activity of RA. Objectives: Analysis of the selection strategy and the “survival” of bDMARDs in patients with RRA. Methods: The retrospective study included data of 95 RRA patients (80 females, 80.8%), aged 23 to 80 years (mean age 57 years), treated with bDMARDs. Mean RA duration was 11.9±7.6 years. All patients were divided into 6 groups depending on the number of the lines of therapy (LOTs) received (from 2 to 7 consecutive bDMARDs). Totally 348 cases of bDMARDs administration were analyzed. Results: TNF-α inhibitors were most commonly used as the first and second lines of therapy: infliximab (INF) – 43 prescriptions, adalimumab (ADA) – 39, etanercept (ETC) – 25, certolizumab pegol (CZP) – 11, golimumab (GLM) - 6. Abatacept (ABA) was prescribed in 32 cases, rituximab (RTM) in 22 cases, and tocilizumab (TCZ) - in 12 cases. The following reasons for bDMARDs discontinuation were identified: lack of efficacy (LE) (55.2% of cases), adverse events (AE), including serious adverse events (14.8% of cases), administrative reasons (10.0% of cases), persistent remission (2.1% of cases), pregnancy (0.6%), and other (17.3% of cases) TNF-α inhibitors were also used in third-line bDMARDs therapies, but preference was given to drugs with a different mechanism of action: ABA-20 patients (23.2%), RTM – 20 (21.1%), TCZ – 15 (15.8%), ETC – 22 (23.2%), ADA – 9 (9.5%), INF – 4 (4.1%), CZP – 3 (3.1%). Treatment was discontinued in 74 patients (77.9%). In this cohort the following reasons for bDMARDs withdrawal were identified: LE (54.1%), AE (17.6%), administrative reasons (9.5%), remission (1.3%), and other (17.5%). The fourth line of therapy was administered in 45 patients: ABA-16 (35.6%), RTM-9 (20%), ADA – 6 (13.3%), TCZ – 5 (11.1%), ETC – 4 (8.9%), CZP – 4 (8.9%), GLM – 1 (2.2%). The reasons for discontinuation (29 patients, 64.4%) were as follows: LE (44.8%), AE (13.8%), other (41.4%). The fifth bDMARDs was used in 3 patients: TСZ-6 (46.1%), RTM – 3 (23.1%), ABA – 1 (7.7%), ETC – 1 (7.7%), ADA – 1 (7.7%), GLM – 1 (7.7%). Therapy was discontinued in 11 patients (84.6%) for the following reasons: LE (45.5%), AE (18.2%), other (36.3%). The sixth line of therapy was necessary in 4 patients: ETC (25%), GLM (25%), CZP (25%), ABA (25%) and was discontinued in 3 (75%) of them due to AE (33.3%) and other reasons (66.7%). One patient received TCZ as the seventh line of therapy. Mean duration of the first line of therapy was 7.6 ± 6.5 months, of the second line - 9.6 ± 7.5 months, of the third line - 11.5 ± 7.1 months, fourth line - 12.5 ± 8 months, fifth line - 13.4 ± 4.8 months, and sixth line - 14.6 ± 4.4 months. Statistical analysis revealed significant differences ( p &lt;0.05) in the mean duration of therapy (retention on therapy) between the 1st and 3rd, as well as the between the 1st and 4th lines of therapy. There were no significant differences in rates of bDMARDs discontinuation due to LE or AE. The rates of bDMARDs discontinuation did not differ significantly in the study groups. Conclusion: The mean retention on a drug in the 3rd and 4th lines of therapy in patients with refractory rheumatoid arthritis was significantly longer than on the 1st line of therapy. The most common reason for bDMARDs discontinuation was lack of efficacy. Additional lines of bDMARDs therapy were not associated with increasing rates of adverse events. Disclosure of Interests: None declared