233. LONG-TERM USE OF RITUXIMAB IN RHEUMATOID ARTHRITIS: 17 YEARS FOLLOW-UP

Abstract

Background: Rituximab (RTX) was first used in rheumatoid arthritis (RA) in an open study of five patients in 1998 at UCLH/UCL. The first randomized-controlled study and subsequent clinical trials confirmed its efficacy and safety profile. The aim of this study was to describe the cohort of 356 patients with RA treated with RTX at UCLH since its first use and to evaluate the long-term safety. Methods: This is a retrospective study of 356 patients with RA who were treated with RTX (1000mg×2) and reviewed in a dedicated weekly RTX clinic. Clinical disease activity at last follow-up for patients currently part of the cohort was determined and adverse events including infusion reactions, infections, neutropaenia, hypogammaglobulinaemia, and interstitial lung disease (ILD) over the follow-up period were collected. Results: Of 356 patients, 80% were female, 20% male. 167 patients were no longer under follow-up due to no response to RTX 20.7%, inadequate response 2.2%, infection 1.1%, hypogammaglobulinaemia 3.3%, infusion reaction 2.8%, deceased 7.6%, care transferred elsewhere 3.9%, other reasons 5.1%. RF was positive in 85.9%, anti-CCP in 77.8%. Patients received a median of 4 cycles of RTX (range 1-18 cycles). RTX was given as monotherapy in 25.3% of patients, concurrently with prednisolone in 7.3%, with DMARDs in 67.7%. Safety analysis was based on 1606.7 patient-years of observation. At cross-sectional review of 189 patients currently followed-up in the RTX clinic, 43.9% were in remission, 13.2% had low disease activity, 32.8% had moderate activity, 7.4% had high disease activity based on DAS28 disease activity scores. The mean HAQ score was 1.400 (range 0-3.000) (87/189 patients). ILD was observed in 8.1% (29/356) patients. Neutropaenia (early and late onset) were observed in 12.4% (44/356). Only 1.7% (6/356) of patients had severe neutropaenia (count ≤0.5×109/L). 18 patients (5.1%) had serology compatible with previous hepatitis B exposure, and there were no reactivations. 1 patient had chronic hepatitis C with no increased viral load or clinical change on follow-up. Shingles reactivation was observed in 2.2%. For patients with recurrent infections prior to RTX (36 patients), 33.3% had no increased frequency of infections, and 66.7% had increased frequency. Other documented side effects included respiratory infections (upper respiratory 5.9%, lower respiratory 21.9%), urinary tract infections 8.7%, skin/soft tissue infections 3.0%. Infusion reactions were documented in 6.4%. Low immunoglobulins (Ig) were noted in 28.6% of patients, IgM being the most common Ig to decrease. Hypogammaglobulinaemia was observed after a mean of 3 cycles of RTX. Conclusion: RTX is a safe and efficacious therapy for RA. A third of patients develop hypogammaglobulinaemia following multiple cycles of RTX, however most of these patients remain stable with no increased risk of infection, and only in a small proportion (3.4%, 12/ 356), RTX had to be discontinued.