Efficacy of MabThera in RA
Evidence for this has been provided by data from the REFLEX (Randomized Evaluation oF Long-term Efficacy of rituXimab in RA) trial, which has also demonstrated significant benefits to patients in terms of the signs and symptoms of RA including reducing swollen joint counts (SJC), tender joint counts (TJC) and fatigue, and improving quality of life (QOL). Furthermore, extension trials from the MabThera pivotal trials have shown that efficacy is maintained or further improved with repeated treatment courses (Cohen et al. 2006; Emery et al. 2006; Moreland et al. 2006 ; Keystone et al. 2006).
Most importantly, the REFLEX trial provides strong evidence that an initial course of MabThera inhibits radiographic progression through statistically significant reductions in total Genant-modified Sharp score, joint space narrowing and erosion scores (Keystone et al. 2006). At 24 weeks, a clear separation of the treatment groups was apparent and changes in the joint space narrowing score had already reached significance. The mean change in joint space narrowing score was 0.5 in the placebo group but only 0.2 in the MabThera-treated group (p=0.016) (Cohen et al. 2006). At 56 weeks, further radiographic improvements were seen, with significant differences observed in the mean change in total Genant-modified Sharp score (p=0.0043), changes in erosion score (p=0.0106) and changes in joint space narrowing score (p=0.0007) between MabThera- and placebo-treated patients (Keystone et al. 2006).
In the REFLEX trial, the primary endpoint (American College of Rheumatology [ACR] 20) measure was achieved. An outstanding score of 51% was obtained for MabThera-treated patients versus 18% for those in the placebo group (p=0.0001) (Cohen et al. 2006). Furthermore, for the secondary endpoints ACR50 and ACR70, the proportion of patients achieving this level of response was also statistically significantly higher for MabThera plus methotrexate patients than for those who received placebo plus methotrexate (ACR50: 27% vs. 5%, p<0.0001; ACR70: 12% vs. 1%, p<0.0001). These results indicate that MabThera is highly effective at relieving the signs and symptoms of RA in patients who have had an inadequate response or intolerance to one or more TNF inhibitors.
MabThera provides impressive benefits for patients by reducing SJC, TJC and fatigue, and by improving QOL. At Week 24 of the REFLEX study, SJC, TJC, pain scores and Health Assessment Questionnaire Disability Index (HAQ-DI) scores were significantly decreased in MabThera-treated patients compared with those receiving placebo. This represents significant clinical improvements in each of these parameters (p<0.0001, p<0.0001, p=0.0045 and p<0.0001 vs. placebo for each comparison, respectively); placebo-treated patients reported little or no clinical improvement in these parameters. MabThera also produces other benefits of importance to patients. Mean Medical Outcomes Study Short-Form (36-item) Health Survey (SF-36) scores for both mental and physical health domains increased to a significantly greater extent in MabThera-treated patients, compared with placebo-treated patients (p<0.0002) (Cohen et al. 2006).
MabThera efficacy is maintained or further improved with subsequent courses of only two infusions in TNF inhibitor IR patients. This includes an enhanced improvement in both mental and physical components of patients’ QOL. When assessed for clinical signs and symptoms of RA, in an open-label extension study, a higher proportion of patients receiving their second MabThera treatment course achieved ACR20, ACR50 or ACR70 responses, low disease activity (DAS28≤3.2) and remission (DAS28<2.6), compared with their first MabThera course (Keystone et al. 2006). In the SF-36, a mean change of 8.7 was observed in the mental component score following the second treatment course, compared with a mean change of 4.8 following the first treatment course (Tak et al. 2006 ). Mean changes in the physical component score of 6.4 and 7.8 were seen at 24 weeks following the first and second treatment courses, respectively ( Tak et al. 2006 ). The current data for subsequent courses of MabThera indicate that there is a trend towards further improvement in response, compared with the first treatment course.