Mabthera-RA 2010

American College of Rheumatology

An ACR response measure that comprises an improvement from baseline of at least 20% in the number of swollen joints on a 66-joint count, tender joints on a 68-joint count and in at least three other ACR criteria. Historically, ACR20 was the primary outcome measure for clinical studies of RA treatment efficacy, but is now being superseded by more stringent definitions of successful therapy.

An ACR response measure that comprises a minimum 50% improvement in the number of swollen joints on a 66-joint count, tender joints on a 68-joint count and in at least three other ACR criteria

A stringent ACR response measure requiring a minimum 70% improvement in the number of swollen joints on a 66-joint count, tender joints on a 68-joint count and in at least three other ACR criteria.

A standardised set of criteria to assess treatment-associated improvements in a patient’s RA signs and symptoms, widely used as efficacy endpoints in clinical studies. The ACR criteria comprise several different measures of RA disease activity, including the number of swollen or tender joints, pain, physical function and various markers of inflammation.

Anti-cyclic citrullinated peptide. Anti-CCP antibodies can suggest a diagnosis of RA.

A substance, typically a protein or a complex sugar molecule, that is recognised by the adaptive immune system.

A process by which macrophages, dendritic cells and other cell types, such as B cells, capture antigens and express them on their cell surface, enabling their recognition by T cells. This process is involved in the development of adaptive immunity.

Acute-phase reactant. A class of plasma proteins that increase or decrease in concentration in response to inflammation, largely due to changes in their production by the liver. Acute-phase proteins include CRP and hepcidin.

Antibodies are manufactured by the immune system in response to, and reacting against, one or more of the body’s own proteins, e.g. RF.

B cells are lymphocytes involved in:

• antigen presentation leading to T cell activation
• autoantibody production
• cytokine production

All three processes are implicated in the pathogenesis of RA.

A group of disease-modifying anti-rheumatic drugs that are derived from biologic molecules such as antibodies or receptors. They modulate the disease process by directly targeting signalling pathways, cytokines, receptors and other mediators contributing to the pathogenesis of RA.

A substance found in the body that can be used as an indicator of biological state. Biomarkers are used as measures of disease activity and can be used to follow disease progression over time. Biomarkers in RA include CRP and RF.

CD20 is a cell surface molecule expressed only on a subset of B cells during their maturation process. By targeting only CD20-positive B cells, MabThera® avoids destruction of stem cells, pro-B cells and plasma cells.

An antibody that is genetically engineered to include polypeptides from different species. MabThera® is a human/mouse chimeric antibody. This combination of proteins confers effective triggering of complement lysis, cell-mediated lysis and CD20-specific binding.

A biochemical cascade that makes up part of the innate immune response. The complement system, and the consequent immune response, can be triggered by rheumatoid factor immune complexes in the synovium.

C-reactive protein. A serum marker of systemic inflammation.

A category of signalling protein involved in intercellular communication.

Dose-ranging Assessment: iNternational Clinical Evaluation of Rituximab in RA. A study examining the efficacy and safety of different MabThera® doses plus MTX, with or without glucocorticoids, in patients with active RA resistant to DMARDs, including biologic agents.

Disease activity score based on 28 joints. A composite numerical score that combines several discrete individual measures of RA activity, such as swollen joint count, tender joint count, ESR and measures of general health status, into a single grading of disease severity. Scores range from 0 to 10. A DAS28 of <2.6 is typically used to define clinical disease remission, although other clinical definitions exist.

Disease-modifying anti-rheumatic drug. Any of a class of therapeutic agents of widely variable structures and mechanisms of action that act on one or more of the underlying causes of RA to slow disease progression. There are two basic categories of DMARD: synthetic or traditional agents, and biologic agents. DMARDs are distinct from symptomatic RA treatments such as NSAIDs or cyclooxygenase-2 inhibitors, which treat pain and inflammation without altering disease progression.

Erythrocyte sedimentation rate. The rate, in mm/hour, at which red blood cells precipitate in uncoagulated blood. The ESR is a common haematological test used as a non-specific measure of inflammation.

European League Against Rheumatism

Criteria developed by EULAR that combine the DAS28 at the time of evaluation with the change in DAS28 between two time points, and enable the user to define improvement or response to treatment. Response categories include good, moderate and no response.

Functional Assessment of Chronic Illness Therapy –Fatigue. A short (13-question) validated standard patient self-report questionnaire designed to measure fatigue and its impact on daily function. The FACIT– Fatigue scale ranges from 0 to 52, with higher scores indicating less fatigue.

The Genant-modified Sharp score focuses on 14 specific sites for evidence of bone erosion and 13 sites for narrowing of the joint space, both key measures of ongoing structural damage to the joints. The maximum score is 290.

A class of steroid hormones synthesised by the adrenal cortex that bind to the glucocorticoid receptor. Glucocorticoids have potent anti-inflammatory effects and are used in the treatment of inflammatory conditions including RA.

Health Assessment Questionnaire. A standardised and widely used patient self-report questionnaire developed to assess the patient's physical function in rheumatic diseases that has since been applied to a wide variety of other clinical fields.

Health Assessment Questionnaire – Disability Index. A sub-category of the full Health Assessment Questionnaire commonly used in RA studies as a measure of disease-associated disability.

Health-related quality of life.

Immunoglobulin. Any one of the proteins used by the immune system to identify and neutralise foreign objects such as bacteria and viruses. Also known as an antibody.

Interleukin-6. The most abundant cytokine in the rheumatoid synovium and an important mediator of fever and the acute-phase response to inflammation.

Inadequate response. Clinically relevant presence of RA signs and symptoms despite undergoing therapy.

Characterised by the loss of articular cartilage. The chronic inflammation of RA is a cause of joint space narrowing.

Manufactured by Genentech and Biogen Idec, and marketed by Genentech and Roche. MabThera^®, called Rituxan^® in the US, is a B cell modulator administered by iv infusion

White blood cells formed by the division of monocytes. Macrophages phagocytose pathogens and produce pro-inflammatory cytokines

Antibodies produced by a single clone of cells or a cell line and consisting of identical antibody molecules

Methotrexate. A synthetic DMARD that acts as an inhibitor of folic acid and of purine metabolism

Non-steroidal anti-inflammatory drug

Pharmacokinetics. The study of the fate of substances following administration to a living organism. Processes involved include absorption, distribution, metabolism and excretion.

Also known as plasma B cells, plasma cells are antibody-producing cells formed following B cell differentiation.

B cells precursors that develop from stem cells. Pro-B cells do not express CD20 and are therefore not depleted by MabThera^®

Rheumatoid arthritis

Randomized Evaluation oF Long-term Efficacy of rituXimab in RA. A study determining the efficacy and safety of MabThera^® (rituximab) plus MTX in patients with active RA who had an inadequate response to TNF inhibitors.

Rheumatoid factor. An autoantibody directed against IgG. About 80% of patients with RA are seropositive for RF, and its presence predicts a more aggressive, destructive disease course.

Simplified Disease Activity Index. A simple assessment of disease activity and treatment response based on the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity (based on a visual analogue scale of 0–10) and level of CRP (in mg/dL).

Swollen Joint Count. The number of swollen joints a patient has at a physician visit, usually based on examination of 66 joints. Used along with other indicators to measure disease activity in RA.

Cells that have the capacity to differentiate into specialised cell types and that can undergo cell division while remaining in an undifferentiated state. B cells develop from haematopoietic stem cells. As stem cells do not express the antigen CD20 on their cell surface they are not targeted and depleted by MabThera^®.

Co-stimulation is required in addition to the antigen-specific signal for T cells to become fully activated. T cell co-stimulation is necessary for T cell proliferation, differentiation and survival.

T cells are lymphocytes that play a central role in adaptive immunity. They are activated by B cells and have a range of functions, including cell-mediated cytotoxicity and the production of pro-inflammatory cytokines.