MabThera(rituximab) Is More Effective In Treating Rheumatoid Arthritis Than Switching Patients To A Second Anti-TNF

Main Category: Arthritis / Rheumatology
Also Included In: Clinical Trials / Drug Trials;  Bones / Orthopaedics
Article Date: 14 Jun 2008 - 12:00 PDT

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New data1 presented at the European League Against Rheumatism (EULAR) annual meeting revealed that when rheumatoid arthritis (RA) patients do not respond to a TNF inhibitor, a commonly used class of drugs in RA, it is more effective to treat them with MabThera (rituximab), than to use a second TNF inhibitor therapy.1 This calls into question the practice of 'cycling' between anti TNFs, and provides evidence that supports preliminary NICE guidance where anti TNF switching has not been recommended.

This data shows that MabThera,with a different mode of action to anti-TNFs, may benefit patients earlier in their treatment pathway. Instead of having to take an alternative anti-TNF, a potentially less effective treatment, using time and NHS budget and risking irreversible damage to their joints, they could benefit from MabThera (rituximab).

The studyi was conducted among 300 patients who had previously not responded to TNF inhibitor therapy. Data at six months showed that MabThera achieved a significantly larger reduction in disease activity (DAS28) than a subsequent anti-TNF agent in patients who had ceased anti-TNF therapy due to lack of efficacy (reduction in DAS28 by 1.55 versus 1.03).

"These findings confirm that switching to an alternative biological agent, such as rituximab, in the subset of RA patients who don't respond to a first anti-TNF agent, can provide major benefits", said Professor Rob Moots, Aintree University Hospitals "In patients with persistent active disease despite anti-TNF therapy, these data suggest that switching to rituximab might be more effective than switching to an alternative anti-TNF agent."

Inhibition of joint damage

New data from another study, REFLEX3, also presented at EULAR, demonstrate that MabThera continues to significantly inhibit the progression of joint damage caused by RA over a period of two years in those patients who do not respond to TNF inhibitor therapy4. X-ray evidence at two years showed that the narrowing of joint spaces and appearance of new bone erosions were reduced by more than 50% in patients receiving MabThera and methotrexate (a commonly used RA drug) compared to patients receiving methotrexate alone (Total Sharp Score increase of 1.14 versus 2.81 respectively, p<0.0001)5. MabThera consistently inhibited progression of joint damage since 89% of MabTheratreated patients who did not show progression the first year had no progression the second year.

Damage to the structure of joints ultimately causes joint destruction and contributes to joint deformity and loss of mobility. The inhibition of joint structural damage is therefore a major goal of treatment. In patients who do not respond to TNF inhibitor therapy MabThera is the first and only therapy to have demonstrated a reduction in joint structural damage.

Patient preference

A new study has been described, assessing the preference (based on a range of treatment preferences and key drivers of choice) for the benefits of a drug modelled on MabThera relative to those of drugs modelled on entanercept Enbrel) and abatacept (Orencia) as a biologic therapy for the treatment of RA. The new data presented at EULAR identified that RA patients prefer treatments with infrequent dosing. The study found that patients favour a treatment model led on MabThera which offers symptom control with less frequency in needing to have treatment.6.

About Rheumatoid Arthritis and MabThera

Rheumatoid arthritis is an autoimmune disease characterised by inflammation that leads to stiff, swollen and painful joints. Current treatments include disease-modifying drugs (DMARDS) and biologic therapy such as the TNF inhibitor drugs.

MabThera is a first-in-class therapy that selectively targets B cells early in the inflammatory cascade of rheumatoid arthritis. B cells are known to play a key role in the inflammation associated with rheumatoid arthritis and MabThera breaks the inflammatory cascade of RA - a series of reactions inflaming the synovia and leading to the cartilage loss and bone erosion that is characteristic of the disease, and may provide an innovative new treatment even in patients with severe and longstanding disease. MabThera has a strong heritage in the treatment of a form of lymphatic cancer called non-Hodgkin's lymphoma (NHL) and the treatments safety profile has now been established in more than a million patient exposures over the last nine years in oncology and more recently rheumatoid arthritis.

MabThera is indicated, in combination with methotrexate, for the treatment of adults with severe rheumatoid arthritis who cannot tolerate or do not respond to anti-TNF therapy.

Safety Profile

The majority of adverse events are mild to moderate in severity. In trials adverse drug reactions occurred with at least a 2% difference compared to the control arm. The most frequent adverse events are infusion reactions which occurred in 15% patients following the first infusion of rituximab and 5% in placebo patients. Fewer reactions are observed with second and subsequent infusions. Severe infusion reactions are uncommon and their frequency is reduced by the use of concomitant IV steroids.

About Roche in Rheumatoid Arthritis

Roche has prioritised research and development of new treatments for auto-immune diseases, including rheumatoid arthritis. Following the launch of MabThera® (rituximab) for RA in 2006 there are a number of projects in development ensuring a rich pipeline including compounds in Phase I, II and III clinical trials. Tocilizumab is the first humanised interleukin-6 (IL-6) receptor inhibiting monoclonal antibody and represents a novel mechanism of action to treat RA, a disease with a high unmet medical need. This treatment is not yet licenced in Europe and is the result of a research collaboration by Roche and Chugai , and is being co-developed globally. Ocrelizumab, a fully humanised anti-CD20 antibody, is just entering Phase III development for RA.

About Roche in the UK

Roche aims to improve people's health and quality of life with innovative products and services for the early detection, prevention, diagnosis and treatment of disease. Part of one of the world's leading healthcare groups, Roche in the UK employs nearly 2,000 people in pharmaceuticals and diagnostics. Globally Roche is the leader in diagnostics, and a major supplier of medicines for the treatment of cancer, transplantation, virology, bone and rheumatology, obesity and renal anaemia. Find out more at http://www.rocheuk.com

A summary of product characteristics is available at http://www.rocheuk.com

References

1 - Finckh, A et al. Which subgroup of rheumatoid arthritis patients benefit most from switching to rituximab versus alternative anti-TNF agents after previous failure to anti-TNF agent? Abstract OP-0249, EULAR 2008

2 - DAS28 is a measurement score used to assess whether a patient shows an improvement in disease activity. DAS28 provides a number on a scale from 0 to 10 which indicates the current activity of the disease.

3 - A Randomised Evaluation oF Long-term Efficacy of rituXimab in RA

4 - Cohen, S et al. Continued inhibition of structural damage in rheumatoid arthritis patients treated with rituximab at 2 tears: REFLEX study. Abstract THU0167, EULAR 2008

5 - As measured by the mean increase from baseline in Total Sharp Score (TSS), an x-ray measurement of change in joint damage

6 - Ostor, AJK et al. Patient preference for rituximab as a treatment for rheumatoid arthritis: a study using discrete choice analysis. Abstract AB0375, EULAR 2008

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