Study: Starting Dose, Cumulative Dose Do Not Predict Rituximab Adherence in RA

Samantha DiGrande

A recently published study explored the impact of 2 different initial doses and a cumulative 2-year dose of rituximab on drug adherence and predictors of adherence to treatment in patients with RA in an observational clinical setting.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that affects the lining of joints, causing a painful swelling that can lead to bone erosion. Rituximab, a commonly used therapy in treating RA, is a chimeric monoclonal antibody directed against CD20 surface antigens expressed on pre-B cells and B cells before their differentiation into plasma cells. A recently published study explored the impact of 2 different initial doses and a cumulative 2-year dose of rituximab on drug adherence and predictors of adherence to treatment in patients with RA in an observational clinical setting.

The study found that initial or cumulative 2-year doses of rituximab used for treatment of RA in this observational clinical setting did not significantly influence long-term adherence to treatment, though concomitant methotrexate use and low DAS28, or disease activity score in a count of 28 joints, at baseline predicted better adherence.

All patients with RA starting rituximab treatment between January 2003 and April 2012 at Skane University Hospital in Scania, Sweden were included in the study, and data on patient treatment characteristics were derived from the South Swedish Arthritis Treatment Register. A total of 153 patients, 74.5% female, were included. The mean age and mean disease duration were 60.7 and 15.8 years, respectively. Percentage of rheumatoid factor- (RF) and anti—citrullinated protein antibody- (ACPA) positive patients were 86% and 82% respectively.

Patients received either 500 mg for 2 doses or 1000 mg for 2 doses administered by intravenous infusion on days 1 and 15, pre-medicated with intravenous methylprednisolone. Seventy-four patients (48%) were started on the 500 mg dose and 79 patients (52%) were put on 1000 mg dose. The decision to initiate biologics and the selection of the starting dosage relied on the treating physician’s judgment, as no formal disease activity level was mandatory.

When appropriate, Mann-Whitney and Chi-Square tests were used in order to compare demographic and treatment characteristics between different starting doses. The level of adherence to the prescribed therapy was measured with drug survival using Kaplan-Meier estimates and Cox-regression analysis.

Infection-free survival or time until the infection started was studied using Kaplan-Meir estimates. The possible baseline predictors were determined using Cox-regression analysis. The predictors were chosen based on clinical relevance and included sex, age, and disease duration (per year increase), presence of RF, CRP, DAS28-ESR (or DAS28 measured with erythrocyte sedimentation rate), and Health Assessment Questionnaire (HAQ) scores, concurrent glucocorticoid use, concurrent methotrexate use, and calendar year of treatment initiation (1998 to 2007).

Of the 153 patients, only 42 received the starting dose but not any continuation of treatment. There was no significant difference for drug adherence when comparing starting doses during the first 5 treatment years, also when adjusted for baseline characteristics. The cumulative doses of the drug at 2 years also did not influence drug adherence. Low DAS28 at baseline and methotrexate use were associated with better drug adherence, however.

The optimal dosing for rituximab in RA has been under debated in past years, and the evidence from dose finding studies in RA are still limited. The results of this study are in accordance with previous studies and recent meta-analyses of randomized clinical trials, showing good response to the lower dose and to repeated treatment. However, more information is needed in order to find a definitive optimal dosing amount of RTX for the treatment of RA.