Background/Purpose:

The optimal retreatment strategy for rituximab is not clear¹. Different strategies are being used in clinical practice, including: on demand retreatment when disease activity increases and fixed interval retreatment. We investigated whether the response duration after the first rituximab course might be used for timing of retreatment by assessing the intra-individual variation in response duration after two subsequent rituximab courses in patients with rheumatoid arthritis (RA).

Methods:

In this retrospective study, RA patients treated with at least three rituximab courses, according to the on demand retreatment strategy, were included. Difference in first and second interval between infusions and between duration until loss of response were analysed with student’s paired t-test, Spearman correlation coefficient and limits of agreement. Date of loss of response was determined by two research physicians based on chart review. 

Results:

Seventy patients were included (table 1). The dosage of the first rituximab treatment cycle was 2 x 1000 mg in 69 patients (in 1 patient unknown), and of the second rituximab cycle 2 x 1000 mg in 57 patients, 2 x 500 mg in 6 patients and 1 x 1000 mg in 7 patients. Concomitant DMARD treatment changes were infrequent and comparable between first and second interval. Forty patients were treated with systemic corticosteroids at baseline; changes in systemic steroid treatment were also comparable between first and second interval.

The mean interval in days was 301 (SD 95) and 341 (SD 123) days for the first and second rituximab interval. Mean time until loss of response was 252 (SD 93) and 307 (SD 126) days respectively. Limits of agreement between 1^st and 2^nd infusion intervals were large, -190 and +272 days (figure 1). Of note, the second interval between infusions  was longer than the first (40 days (SD 119) p = 0.003).

Conclusion:

Duration of response after the first rituximab course is not a useful parameter in timing of retreatment, because of the large intra-individual variation in response duration. The second rituximab interval seems to be longer than the first, which could lead to increasing overtreatment when fixed schedule retreatment is used.

Reference list:

1.      Buch MH, Smolen JS, Betteridge N, et al. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis 2011;70:909-920.

Table 1: Baseline characteristics

anti-CCP= anti-cyclic citrullinated peptide; DAS28 = 28 joints disease activity score;

RTX = rituximab; DMARD = disease-modifying antirheumatic drug;  MTX = methotrexate