Objectives
B cell depletion therapy based on rituximab in patients with rheumatoid arthritis (RA) was pioneered at UCLH/UCL in 1998. The objective of this study was to evaluate long-term persistence of rituximab and identify factors associated with discontinuation of treatment.
Methods
Retrospective review of medical records from all rituximab-treated RA patients followed up in a dedicated clinic (1998–2020). Data collected included gender, disease duration, previous DMARDs, autoantibody status, age and concomitant therapy at first cycle, length of follow-up, number of cycles. Drug survival and factors associated with drug discontinuation were analysed using Kaplan-Meier survival curves, logrank test and Cox regression analysis.
Results
A total of 404 patients were included. Median disease duration and age at time of first rituximab cycle were 10 and 57 years, respectively. Median total follow-up was 55 months and median number of cycles five. 93.1% of patients were seropositive. 31.2% of patients stopped RTX, with the largest reason for discontinuing being primary inefficacy (42.1%). Comparison of Kaplan-Meier curves showed that rituximab drug survival was lower in seronegative patients and in patients who had previously failed at least one biologic DMARD (bDMARD). Cox regression analysis revealed that RTX discontinuation was associated with a greater number of previous bDMARDs.
Conclusion
Many patients with RA achieve good control of their disease with repeated cycles of rituximab treatment. The most common reasons for treatment discontinuation were either primary or secondary inefficacy. Patients who were seronegative and who had previously failed other bDMARDs were more at risk of drug discontinuation.
Background
B-cell depletion therapy based on rituximab in patients with seropositive rheumatoid arthritis (RA) was pioneered at UCLH/UCL in 1998. The positive results of the initial open-label UCLH/UCL trials led to the Phase IIa proof of concept trial confirming efficacy and safety for rituximab in the treatment of patients with RA. A Phase III trial followed and licensing in 2006. We report a service evaluation of the UCLH/UCL cohort of RA patients treated with rituximab over the last 20 years.
Methods
A retrospective review of electronic records from all patients with RA treated with rituximab followed up in a dedicated clinic at UCLH/UCL (1998-2019) were included. Data on gender, age at first treatment, previous DMARDs, concomitant therapy at the time of the first rituximab cycle, total number of rituximab cycles and length of follow-up while on rituximab were collected. For patients currently on rituximab, further information was collected at last follow-up, including concomitant therapy, swollen and tender joint count, global VAS, CRP and ESR. DAS28ESR was calculated.
Results
296 patients had received rituximab therapy since November 1998, with 105 remaining on rituximab at final data collection (14/10/2019). Median follow-up was 77.5 months. Clinical data is shown in Table 1. Information for previous DMARDs was only available for 196 patients in the whole cohort, and for 70 patients currently on rituximab. The most common concomitant DMARD at first cycle was methotrexate with a similar percentage receiving methotrexate at last follow-up. The median number of previous DMARDs were 4 and 3 respectively. Within both cohorts approximately 31% of patients received rituximab as their first biologic.
Conclusion
This retrospective service evaluation of 296 patients with RA who had undergone rituximab therapy since 1998 showed that more than one third remained on rituximab at last follow-up. Of these, 70.2% of patients were in clinical remission or with low disease activity. Most patients (94%) remaining on rituximab were receiving only 1 or no concomitant therapies. Multiple cycles of treatment with rituximab have thus proved to be an effective therapeutic strategy for patients with RA resulting in long-term and highly favourable control of their disease.
Disclosures
C.M. Norris-Grey None. S. Moore None. G. Cambridge None. V. Reedy None. M. Leandro Consultancies; Genentech: consultancy fees for attending meeting on obinutuzumab trial in lupus nephritis.
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