Rheumatoid Arthritis Flare Up Reduced with Rituximab

As needed treatment rituximab (RTX) regimens lead to delayed retreatment and disease flare up in a large proportion of patients with rheumatoid arthritis (RA), according to findings published in the Journal of Clinical Rheumatology.

A team of researchers recruited 151 RA patients in Finland between April 2005 and December 2011 for a 12 month follow up study in order to assess the clinical response of RTX treatment. The patients were included if their Disease Activity Score was 28 or higher and they matched the European League Against Rheumatism (EULAR) response criteria. Additionally, the patients were required to reach disease remission (DAS 28 < 2.6) or low disease activity (DAS 28 < 3.2) to be included in the analysis.

Three-quarters of the patients were women and 89 percent were seropositive (defined by rheumatoid factor and/ or anti cyclic citrullinated peptide antibodies). The median disease duration for all patients was 15 years and the patients had previously used an average of 6 disease modifying anti rheumatic drugs (DMARDs). Nearly all patients had used DMARDs in combination, most commonly methotrexate (MTX, 97 percent), followed by hydroxychloroquine/ chloroquine (95 percent), sulfasalazine (91 percent), aurothiomalate (74 percent) and leflunomide (69 percent).

The patients received RTX on days 1 and 15 as a 1000 mg intravenous infusion with intravenous methylprednisolone premedication. RTX was administered upon a disease flare up incident. In 17 patients, RTX treatment was initiated with 500 mg of RTX separated by 2 weeks. Most of those patients received 1000 mg RTX as retreatment. The researchers used EULAR response criteria to determine RTX response after a minimum period of 3 months.

There were 128 patients who received 2 courses, 76 patients who received 3 courses, and 42 patients who received 4 courses of RTX retreatment over the duration of the study period. The mean time to retreatment for the first 4 courses varied between 11 and 13 months, the researchers found. The median DAS 28 decreased from 5.4 to 3.3 after the first RTX retreatment. After the second RTX treatment, DAS 28 was 3.1. Between the second and third RTX retreatment doses, the baseline DAS 28 score was 4.6 and 4.24, respectively. The researchers added that the previously failed tumor necrosis factor inhibitors were not relevant to RTX in this patient population.

“Recent evidence shows that the more aggressive ‘treat to target’ approach for RTX treatment leads to more effective disease management without compromised safety profile compared with treatment as needed (PRN) strategy,” the authors said. “The PRN approach used in this study cohort led to delayed RTX retreatment and disease flare in a significant proportion of patients. Thus, a regular retreatment every 6 months, at least, after the first 2 treatment courses in patients who are not in remission could allow better control of disease activity.”

The researchers noted 2 related fatalities during the study as well as 82 serious adverse events (12 related and 70 unrelated). There were 11 patients who discontinued the study from adverse events, and sometimes in combination with lack of efficacy, the researchers reported.