Background/Purpose: Rituximab (RTX) is an effective and relatively safe treatment for rheumatoid arthritis (RA). Following treatment, controversy remains on how best to optimise further retreatment while limiting risks of cumulative immunosuppression and cost. At UCLH/UCL RA patients are offered individualized preventive retreatment with RTX based on the duration of their response to initial treatment. This strategy, while allowing continued control of disease activity in many patients with flare prevention may lead to patient overtreatment. The aim of this study was to identify predictors of flare in patients with RA 1 month prior to RTX retreatment.

Methods: A prospective study of 18 RA patients retreated with RTX preventively, were assessed 4 weeks prior to scheduled RTX retreatment where clinical and laboratory assessment, US of wrists and small joints of the hands were performed. Patient reported outcomes (PROs) (HAQ (health assessment questionnaire), Facit-F (functional assessment of chronic illness therapy), SF-36 (short form health survey), EuroQol 5D 3L) were completed weekly until RTX retreatment 4 weeks later. At this time point clinical assessment and US scan were repeated. The study is ongoing.

Results: We have so far studied 11 females and 7 males, with a mean age of 64 years. The patients were assessed at mean 7.2 months after their previous RTX treatment. At initial assessment (week 0) 66.7% (12/18) of patients remained depleted (CD19 count <0.005) while 33.3% (6/18) had already started repopulating. ESR and CRP increased, decreased or remained stable as shown in Figure 1. The number of joints with synovial hypertrophy (SH) on US increased in 61.1%, and decreased in 27.8%. The number of joints showing power Doppler (PD) increased in 27.8%, and reduced in 33.3%. All patients with PD (9/18) on US, reported worsening of their joint pain and/or early morning stiffness. Surprisingly, the general VAS and DAS28 scores decreased by13.3% and 34.9% respectively in the majority of patients, (44.4% and 77.8% respectively) from week 0 to week 4. The weekly PROs were completed by 9/18 patients. HAQ, Facit-F and physical component summary (PCS) of SF-36 scores showed similar changes. The mental component summary (MCS) of SF-36 increased in 33.3% with no change in 44.4%. EuroQol 5D 3L scores increased in 22.2%.

Figure 1. Percentages of all variables changing from week 0 to week 4.

Conclusion: The data of this study which is ongoing, does not show any consistent pattern of variation within 4 weeks prior to RTX retreatment, and baseline assessments at week 0 did not seem to predict stability or worsening of symptoms in the following 4 weeks. The variables increased, decreased or remained the same in almost similar patient numbers. The ESR, CRP and SH on US showed an increase over the 4 week period. All patients with PD on US reported symptoms. Assessment of patients 1 month before preventive retreatment with RTX does not seem to be able to predict which patients are likely to be flaring shortly.