AB0219 EXPLORING LONG-TERM DRUG EFFECTIVENESS AND DRUG SURVIVAL FOR RITUXIMAB REFERENCE DRUG IN TREATMENT OF RHEUMATOID ARTHRITIS PATIENTS IN ORDINARY OUTPATIENT CLINIC

Abstract

Background:In randomized controlled trials (RCTs) rituximab (RTX) has been shown to effectively suppress inflammation and reduce structural joint damage in rheumatoid arthritis (RA) patients [1]. There is a lack of RA data on RTX effectiveness and drug survival when used in real life practice.Objectives:To explore long-term drug effectiveness and drug survival for RTX used to treat RA patients in ordinary clinical practice.Methods:The study population included RA patients treated between 2006 and 2020 with RTX at an outpatient clinic in Norway. Patients were monitored using recommended measures for disease activity and patient reported outcomes (PROs). Drug effectiveness was assessed with random intercept linear mixed models. Drug survival was described using Kaplan-Meier survival analysis. Baseline predictors of drug survival were assessed with multivariable Cox proportional hazard models.Results:In database a total of 246 RA patients (females 74.8%) were identified to have been treated with RTX. At baseline mean (SD) age was 59.1 (13.5) years, disease duration 13.0 (10.2) years, RF positive 88.8%, ACPA positive 92.1%. Majority of patients had first cycle RTX dosage of 2000 mg (82.9%). At baseline patients currently using conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were 51.5% (methotrexate 39.4%), prednisolone 73.6% and a total of 17.1% were biologic DMARDs (bDMARDs) naïve. In table 1 mean (SE) values for disease activity and PROs are shown for baseline and subsequent years after baseline for 5 years follow up.Table 1.Changes in disease activity and PROs at baseline and subsequent 1-year periodsBaselineN=2461 yearN=2462 yearN=2043 yearN=1634 yearN=1305 yearN=111CRP (mg/L)23.1 (2.1)21.3 (1.6)11.7 (0.9)8.6 (1.4)6.2 (0.7)6.7 (0.9)ESR (mm/hr)32.1 (1.4)31.1 (1.3)22.3 (1.1)17.6 (1.2)14.3 (1.0)13.6 (1.2)SJC28 (0-28)6.3 (0.4)5.4 (0.3)3.2 (0.3)2.2 (0.2)1.6 (0.2)1.5 (0.2)TJC28 (0-28)7.1 (0.4)6.6 (0.3)3.6 (0.3)2.6 (0.3)2.2 (0.3)1.8 (0.3)DAS284.9 (0.1)4.7 (0.1)3.6 (0.1)3.1 (0.1)2.8 (0.1)2.7 (0.1)CDAI22.9 (0.9)20.7 (0.7)12.3 (0.7)9.4 (0.7)8.5 (0.6)7.7 (0.7)PGA (0-100mm)57.2 (1.7)53.7 (1.4)38.1 (1.6)33.7 (1.9)35.0 (2.1)32.8 (2.2)MHAQ (0-3)1.0 (0.0)0.9 (0.0)0.7 (0.0)0.6 (0.0)0.5 (0.0)0.5 (0.0)During follow up all disease activity and PRO measures improved significantly (p <0.001). Least improvement was seen in first year and a more substantial improvement progressed since second year. Percentage of patients with no, moderate and good treatment response defined according to EULAR response criteria [2] is shown in figure 1.Figure 1.No, moderate and good response to RTX treatmentNo significant difference during the 5-year follow-up was found regarding previous use of bDMARD or not and for concomitant use of csDMARDs or not for variables listed in the table 1.Drug survival for the RTX was 83% (95CI 77-87%) after 1 year, 66% (95CI 60-72%) after 2 years, 53% (95CI 46-59%) after 3 years, 46% (95CI 39-52%) after 4 years and 34% (95CI 28-40%) after 5 years of follow up.No significant difference in drug survival was found between bDMARD naïve and previous users of bDMARDs or between concomitant and non-concomitant users of csDMARDs. RF positive patients had a better drug survival.In prediction analysis RF positive status, high baseline DAS28, low baseline CRP, previous bDMARDs use, short disease duration and low MHAQ were found to be independently associated with better drug survival.Conclusion:Our real life data shows that RTX treated RA patients had a satisfactory treatment response and drug survival declines rather linearly over time. However, a significant treatment response was achieved primary in the second year indicating that at least 2 twin infusions should be given before identifying treatment failure.