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American College of Rheumatology

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 Historically, ACR20 was the primary outcome measure for clinical studies of RA treatment efficacy, but is now being superseded by more stringent definitions of successful therapy.

Similar to ACR20 but constituting a minimum 50% improvement in swollen joint count, tender joint count and at least three other criteria.

A stringent ACR response measure, defined as for ACR20 and ACR50 but requiring a minimum 70% improvement. An ACR70 response is sometimes used to refer to a state of clinical remission, although clinical remission is a status rather than a change of disease activity.

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.

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.

The recognition and response by the immune system to challenge with specific antigens. The adaptive immune response provides the body with the ability to recognise and remember new pathogens and is responsible for the development of long-lasting, protective immunity.

Alanine aminotransferase

Acronym for ACTEMRA versus Methotrexate double-Blind Investigative Trial In mONotherapy. A randomised, double-blind, placebo-controlled study in 673 patients with moderate to severe RA comparing ACTEMRA/RoACTEMRA monotherapy versus methotrexate monotherapy.

Analysis of variance

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

Aspartate aminotransferase

An adaptive immune response to antigens present in the body’s own tissues and so directed against part of the body itself.

An antigen present on the body’s own endogenous tissues, involved in the development of autoimmunity.

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. Current biologics include anti-TNFs (adalimumab, etanercept, infliximab, golimumab, certolizumab),
B-cell targeted therapies (rituximab),
a T-lymphocyte co-stimulation modulator (abatacept) and an IL-1 inhibitor (anakinra).

Complete blood count

Cyclic citrullinated peptide – anti-CCP antibodies can suggest a diagnosis of RA.

A Dutch clinical study with the name COmbinatietherapie Bij Reumatoïde Artritis study – a randomised double-blind strategy trial of initial intensive combination treatment which demonstrated that step-down combination therapy with prednisolone, methotrexate and sulphasalazine was superior to sulphasalazine monotherapy for suppressing disease activity and radiological progression of RA.

C-reactive protein – a serum marker of systemic inflammation.

A category of signalling protein involved in intercellular communication. Cytokines include TNF-α and IL-6, which trigger inflammation.

Disease activity score in 28 joints – a composite numerical score which 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, though other clinical definitions exist.

Disease-modifying anti-rheumatic drug – any of a class of therapeutic agents of widely variable structures and mechanisms of action which 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.

European Medicines Agency

Manufactured by Amgen. Marketed by Amgen/Wyeth. Enbrel is an anti-TNF administered subcutaneously, once or twice weekly.

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.
There is also a more detailed fatigue questionnaire called FACIT-F.

(United States) Food and Drug Administration

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 total score has 584 increments of 0.5 points, for a total maximum score of 292.

Glycoprotein 130. IL-6, once bound to the IL-6 receptor, then binds to this transmembrane protein, resulting in IL-6 signal transduction.

Health Assessment Questionnaire – a standardised and widely used patient self-report questionnaire developed to assess the patient's physical function in rheumatic diseases and since 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.

Haemoglobin – a protein found in red blood cells that carries oxygen. RA can lower the levels of Hb, leading to anaemia.

A hormone produced by the liver that is a key regulator of iron metabolism and a mediator of anaemia of inflammation.

Manufactured and marketed by Abbott. Humira is an anti-TNF administered via subcutaneous injection twice a month.

Immunoglobulin

Interleukin – any of several compounds produced by cells of the immune system that function in the regulation of the immune system.

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

IL-6 receptor

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

A response that is crucial during the early phase of host defense against infection by pathogens, before the antigen-specific adaptive immune response is induced.

Circumscribed loss of bone substance due to juxta-articular osteoporosis or invasion of pannus, a sheet of proliferating fibrous tissue that contains inflammatory cells. Pannus development can also lead to joint space narrowing as a result of cartilage destruction and bone erosion.

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

Acronym for TociLIzumab Safety and THE Prevention of Structural Damage. A randomised, double-blind, placebo-controlled study in 1,196 patients with moderate to severe RA who had an inadequate response to methotrexate, comparing ACTEMRA/RoACTEMRA plus methotrexate versus placebo plus methotrexate.

Lower limit of normal

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

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

Membrane IL-6 receptor

Non-steroidal anti-inflammatory drug

Acronym for tOcilizumab Pivotal Trial in methotrexate Inadequate respONders. A randomised, double-blind, placebo-controlled study in 623 patients with moderate to severe RA who had an inadequate response to methotrexate, comparing ACTEMRA/RoACTEMRA plus methotrexate versus placebo plus methotrexate.

Manufactured and marketed by Bristol–Myers Squibb. Orencia is a T-cell co-stimulation modulator, which inhibits T-cell activation by binding to CD80 and CD86, thereby blocking interaction with CD28. It is administered by IV infusion.

An aggressive front of tissue in RA-affected joints that invades and destroys local articular structures.

Pharmacokinetic

Rheumatoid arthritis

Acronym for Research on ACTEMRA Determining effIcacy after Anti-TNF failurEs. A randomised, double-blind, placebo-controlled study in 499 patients with moderate to severe RA who had an inadequate response to anti-TNFs, comparing ACTEMRA/RoACTEMRA plus methotrexate versus placebo plus methotrexate.

Manufactured and comarketed by Centocor and Schering-Plough. Remicade is an anti-TNF administered by IV infusion.

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 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).

Medical Outcomes short form-36^® – a quality-of-life questionnaire that measures a patient’s physical function as well as their mental or psychological function. SF36 consists of 36 items and eight scales, from which two summary scores can be extracted: the physical component and the mental component scores. The scores range from 0 to 100 (higher scores indicating better health).

Soluble IL-6 receptor

A joint that is swollen on physical examination.

Synovium (or synovial membrane) is the connective-tissue membrane that lines the inner side joint capsule and secretes synovial fluid (or synovia).

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.

An inflamed joint that is painful when pressed.

Tumour necrosis factor – a cytokine involved in the inflammatory reaction of the immune system.

Acronym for Tocilizumab in cOmbination With traditional DMARD therapy. A randomised, double-blind, placebo-controlled study in 1,220 patients with moderate to severe RA who had an inadequate response to DMARD therapy, comparing ACTEMRA/RoACTEMRA plus DMARD(s) versus placebo plus DMARD(s).

The type of transmembrane signalling that occurs when IL-6 binds to soluble IL-6 receptor and subsequently to membrane-expressed gp130. Trans-signalling can induce a signal in a cell that does not express the IL-6 receptor.

Upper limit of normal