Treatment to target improves rituximab RA efficacy
MedWire News: Rituximab retreatment should be given to rheumatoid arthritis (RA) patients using a treatment-to-target (TT) protocol, suggest UK researchers who believe this has greater efficacy than a treatment-as-needed (PRN) regimen.
Second and subsequent treatments with the therapeutic monoclonal antibody rituximab were originally given at the discretion of the treating physician and on swollen joint counts. However, later studies have followed a 24-week regimen, with further treatment given to patients who do not meet the the Disease Activity Score criteria for remission in 28 joints based on an erythrocyte sedimentation rate below 2.6 (DAS-28-ESR< 2.6).
To compare the efficacy and safety of the two approaches, Paul Emery (University of Leeds) and co-workers recruited 493 RA patients to with an inadequate response to methotrexate who participated in rituximab phase II or III studies.
The patients were assigned to receive open-label intravenous rituximab 2 x 1000 mg at 2-weekly intervals plus methotrexate.
Rituximab was given to 236 patients using the TT approach, and to 257 patients on a PRN basis with treatment for 24 weeks or longer according to physician discretion for the first course, and 16 weeks or longer for subsequent courses where patients had eight or more swollen and tender joints.
Both regimens achieved or improved patient response, but TT consistently produced greater improvements in DAS-28-ESR score compared with PRN from weeks 24 to 110, with significant differences seen from week 40. Health Assessment Questionnaire-disability scores were consistently and significantly lower in patients following TT than PRN after week 56.
TT led to a significantly higher proportion of patients achieving a major clinical response than PRN (12.3 vs 5.1%), and patients following the TT regimen were significantly less likely to experience RA flare over five courses of rituximab (7-34 vs 54-84%).
The TT patient group had more retreatment than the PRN group, with 977 patient-years exposure over maximum of 7.4 years versus 450 patient-years over 2.8 years. Although there was a higher rate of overall adverse events with TT (364.3 vs 255.0 per 100 patient-years), the TT and PRN groups did not significantly differ in terms of serious adverse events (12.0 vs 16.0 per 100 patient-years) or serious infections (2.2 vs 3.4 per 100 patient-years).
"It can be concluded that retreatment with rituximab, based on 24-week evaluations and treatment to a target of DAS-28-ESR remission, leads to improved efficacy and tighter control of disease activity compared with a PRN regimen," Emery et al report in the journal Rheumatology.
"Rituximab TT may be the preferable regimen for the treatment of patients with RA."
By Lynda Williams