Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab

Abstract

Objectives The REDO trial showed that ultra-low dose rituximab (500 mg or 200 mg) was similarly effective in the majority of rheumatoid arthritis (RA) patients. This pre-planned secondary analysis investigates 1) associations between rituximab dosage, drug levels, anti-drug antibodies (ADA) and B cell counts and 2) the predictive value of pharmacokinetic and -dynamic parameters, patient, disease and treatment characteristics in relation to response to ultra-low dose rituximab. Methods For 140 RA patients from the REDO trial, differences in drug levels, ADA and B cell counts were examined at baseline, three and six months after dosing. Treatment response was defined as absence of flare and no extra rituximab or > 1 glucocorticoid injection received during follow-up. The association between potential predictors and response was investigated using logistic regression analyses. Results Lower doses of rituximab resulted in lower drug levels but did not significantly affect ADA levels and B cell counts. 3 (10.7%), 12 (20.7%) and 7 (13.0%) patients failed to meet response-criteria in respectively the 1000 mg, 500 mg and 200 mg group. Drug levels, ADA and B cell counts as well as patient, disease and treatment characteristics were not predictive for response to ultra-low dose rituximab. Conclusion Results of this study further support that continued treatment with 500 or 200 mg rituximab is similarly effective as 1000 mg in RA patients doing well on rituximab. These results, combined with absence of clinical dose response relation in the original REDO study, suggest that 200 mg rituximab is not yet the lowest effective rituximab retreatment dose in RA.

Identification of Covariates Modulating B‐Cell Repopulation Kinetics in Subjects Receiving Rituximab Treatment

“…This likely indicates that rituximab is applied at saturation in our study population. As other previous studies demonstrate similar clinical efficacy of lower rituximab doses in AAV and RA (30,31), our findings encourage further studies investigating the clinical efficacy of low-dose rituximab treatment in autoimmune diseases, especially in long-term use for remission maintenance.…”

Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis

“…The association between 200 mg RTX and positive response after two-dose and three-dose vaccination could be explained by faster B cell repletion. Previous studies showed The RTX-COVAC-2 study that B cell repopulation is associated with humoral response [3,9] and that B cell numbers are non-significantly higher at 6 months after a dose of 200 mg RTX compared with 1000 mg [10]. Unfortunately, B cell counts were not performed in our current study.…”

Patients' and rheumatologists' perceptions on dose reduction of rituximab in rheumatoid arthritis

“…To mitigate this insecurity, rheumatologists indicated a need for predictors of successful dose reduction. Although Vital et al demonstrated that the degree of B-cell depletion determines the clinical response more strongly than the dose of rituximab (Vital et al, 2011), recent research has not been able to identify significant predictors for the response to ultra-low doses of rituximab (Wientjes et al, 2022). The lack of experience with rituximab among our participating rheumatologists might in turn be explained by perceptions about other available advanced therapies, as Belgian rheumatologists perceived an intravenous administration route as less satisfactory for patients in terms of disease control compared to subcutaneous administration of bDMARDs (De Mits et al, 2016).…”