Basel, 17 June 2010
Roche's MabThera is the first and only licensed biologic to offer a targeted B cell approach to rheumatoid arthritis (RA) treatment
Patients treated with MabThera experience significant improvement in disease activity when treated every 6 months
Experts at this yearâ??s European League Against Rheumatism (EULAR) annual congress highlighted to rheumatologists that targeted treatment in RA, through the testing of specific blood markers at the time of diagnosis, could have a significant impact on treatment decisions, resulting in an improvement in patient quality of life.
Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), two characteristic autoantibodies produced by autoreactive B cells, are found in approximately 80% of RA patients. For these patients, MabThera could potentially provide greater benefits. Data from a pooled cohort of two MabThera Phase III studies showed that patients who tested positive for either RF or anti-CCP (known as seropositive), were two to three times more likely to achieve a 70% improvement in their symptoms (ACR70) when treated with MabThera than those who did not have these autoantibodies (20.9% seropositive patients achieved ACR701 vs. 6.9% seronegative patients).i
As a selective B cell targeted therapy, MabThera is the first and only targeted treatment option available for RA.i Additional biomarker analyses from other MabThera Phase III studies are pending.
â??Biomarkers can help us identify RA patients that will have a good response to treatment with MabThera. This has positive implications in terms of clinical practice. By treating patients with the best option for their disease, we can bring RA under control more rapidly and preserve function, reduce pain and maintain higher quality of life for patientsâ?, said Professor John Isaacs, Newcastle University, UK.
Achieving remission with MabThera treatment
Additional data presented at EULAR shows that tighter control of disease activity can be achieved with MabThera if patients are assessed every six months and continuous treatment given, when remission2 has not been achieved. Following this treatment regime, more than twice as many patients (12.3% vs. 5.1%) achieved a major clinical response, defined as an ACR70, for at least 6 consecutive months.ii
Further, patients treated to achieve remission benefited from greater improvements in disease activity (measured by DAS28-ESR) and physical function (assessed by the Health Assessment Questionnaire-Disability Index) compared to those treated at the physicianâ??s discretion.
Nearly a decade of safety data
A post hoc analysis from pooled clinical trials supports that MabThera in combination with methotrexate (MTX), is well tolerated over multiple courses of treatment and is comparable to treatment with MTX alone. The most frequent adverse events in the MabThera group were infusion-related reactions (IRR) and the majority occurred after the first infusion of the first course (23%) with 0.5% considered serious (over all courses of treatment). Rates of serious adverse events and infections generally remained stable over time and between treatment courses. The overall serious infection rate was comparable to that observed in the placebo population. These data, from over 3,000 patients, provide important cumulative safety information, adding to the wealth of existing studies defining MabTheraâ??s safety and its use as a long-term treatment option for RA.iii
In another updated analysis, data from 283 patients showed that the incidence of serious infections in those who received biologics after being treated with MabThera did not increase.iv The rate and types of serious infections was consistent with that seen in the long-term safety analyses.iii
More information about the studies
Isaacs, J et al. Biomarkers study
A post-hoc analysis looked at a pooled cohort from 2 Phase III studies, which included patients where MabThera was added to existing methotrexate (MTX), the current standard RA therapy. MabThera was given by IV infusion on days 1 and 15. A total of 670 patients were included in the pooled analysis. The research determined the serological status of patients by analysing the presence of specific autoantibodies (RF and anti-CCP), and compared the clinical outcomes at weeks 24 and 48 of those who were seropositive (those who tested positive for RF and/or anti-CCP) to those who were seronegative. The measures included ACR and EULAR responses, as well as DAS28 scores. Both groups of patients (seropositive and seronegative) were seen to benefit from treatment with MabThera, however, the response was enhanced in the seropositive population.
At week 24, seropositive patients were more than twice as likely to achieve an ACR response (ACR20 or ACR50) than those who were seronegative. At week 48 seropositive patients were over three times more likely to achieve a 70% improvement in symptoms (ACR70) compared to seronegative patients (20.9% vs. 6.9%). Seropositive patients also had significantly greater reduction in DAS28, and were more likely to achieve a low disease status by week 48.
Emery, P et al. Repeat treatment at 6 months
The analysis assessed patients in Phase II or III studies of MabThera who had previously had an inadequate response to MTX. Patients were treated with repeat courses of MabThera 2 x 1000mg, on days one and fifteen, according to two treatment approaches. The first approach was to retreat patients every 6 months if the DAS28 was greater than or equal to 2.6 (treating to remission) , whilst the second approach was for repeat treatment to be administered at the physicianâ??s discretion after a minimum of 16 weeks, if both swollen joint count and tender joint count were more than eight.
Patients treated to remission benefited from tighter control of disease symptoms and improved physical function (HAQ-DI) compared to those treated at the physicianâ??s discretion (ACR70 for 6 consecutive months of 12.3% vs. 5.1% respectively).
Van Vollenhoven, RF et al. Long-term safety study
A post hoc analysis of pooled data from patients treated with MabThera in combination with MTX in a global clinical trial programme was conducted. 3189 patients have been treated with MabThera/Rituxan, providing 9342 patient years experience, including nine years follow-up with up to 15 courses of treatment. Over 1500 patients have been followed for more than three years and 2417, 1724, 1392 and 1036 patients received >2, >3, >4 and >5 courses of treatment respectively. The findings support that MabThera continues to be well-tolerated, with the rates of serious adverse events and infections remaining stable over time and between courses of treatment based on an observed case analysis.
Genovese, M et al. Rate of serious infection in RA patients who receive biologic treatment after discontinuing MabThera
In this updated analysis, the rate of serious infections was evaluated in patients to determine whether the B cell depletion following treatment with MabThera may have an impact on the safety of treatment with a different biologic following discontinuation of treatment with MabThera. Analysis showed that in the 283 patients subsequently treated with a biologic post Mabthera (the majority of which were TNF-antagonists), the rate of serious infection events (SIE) was not increased. Overall, the types of infections were typical for RA patients and consistent with rates seen in other safety analysis.
