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Objectives: The first aim of this master thesis was to develop a prospective study protocol investigating tapering and different retreatment strategies of rituximab, looking at effectiveness, safety and patient-reported outcomes. Before conducting a randomised controlled trial, a clearer view on the current situation and patient characteristics was necessary. Therefore, the second aim was to analyse the daily practice effectiveness and safety of rituximab in rheumatoid arthritis to further optimise the development of the prospective study protocol. Methods: A retrospective single-center cohort study was conducted in patients with rheumatoid arthritis previously or currently treated with rituximab at the division of Rheumatology, University hospitals Leuven. Data were collected from baseline (01/01/2006) till rituximab discontinuation, death or the end of the data collection (01/12/2019), whatever comes first. Baseline is defined as the moment on which there was decided to start rituximab treatment. Data on demographics, previous rheumatoid arthritis treatment, concomitant medication, disease activity, patient-reported outcomes, dose, number of cycles and adverse events related to rituximab were collected. Drug survival and associated parameters were analysed using the Kaplan-Meier analysis, log-rank test and Cox regression analysis. EULAR responses, defined as the difference in DAS28-CRP/ESR score between baseline or retreat decision and week 16, were calculated for cycle 1 and cycle 2 to evaluate the effectiveness. Spearman correlation was used to investigate a correlation between CD19-levels and DAS28-CRP at any timepoint during the cycle, measured from 01/12/2016 till 01/12/2019. Results: This retrospective study included 104 patients. The median (IQR) follow-up time of the patients was 39.5 (14.3-80.8) months. The median (IQR) interval between cycles increased from 8.0 (6.0-11.0) months (time between cycle 1 and cycle 2) up to 10.0 (7.5-13.5) months (time between cycle 2 and cycle 3) and 13.6 (8.0-16.0) months (time between cycle 3 and 4). The Kaplan-Meier analysis showed an estimated rituximab survival of 77.4% after 127 months from baseline. Cox proportional hazard regression showed that an increasing number of previously used bDMARDs and being female were significantly associated with a lower drug survival. Older patients, patients with erosions and ACPA-positive patients had a higher chance to continue rituximab. At week 16 of cycle 1, 15 (15/71, 21.1%), 25 (25/71, 35.2%) and 31 (31/71, 43.7%) patients showed a low, moderate and good EULAR response respectively and at week 16 of cycle 2, 15 (15/60, 25.0%), 19 (19/60, 31.7%) and 26 (26/60, 43.3%) patients showed a low, moderate and good EULAR response respectively. The Spearman correlation test showed no significant correlation between DAS28-CRP and CD19-level. Only 14 patients (14/104, 13.5%) had rituximab related adverse events. Most frequent adverse events were infections related to rituximab. Conclusion: This retrospective study showed that rituximab can be considered as a highly efficacious drug with increasing intervals between cycles and without major side effects related to rituximab. Survival analysis and EULAR response proved that rituximab is an efficacious drug. A fixed-interval retreatment strategy needs further investigation.