Biological Agents As A Treatment of Rheumatoid

Arthritis Abdullatiff Sami Al-RashedConnective Tissue Disorders Elective212516770College of Medicine, King Faisal UniversityAl-Ahsa, Saudi Arabia

Introduction • Biologic Agents are drugs that are genetically

engineered from a living organism, such as a virus, gene or protein, to simulate the body’s natural response to infection and disease.

• They target proteins, cells and pathways responsible for the symptoms and damage of rheumatoid arthritis and other types of inflammatory arthritis.

Types

TNF Inhibitors

1. Etanercept– It is a recombinant version of soluble human TNF receptor that

binds specifically to tumour necrosis factor and blocks its interaction with endogenous cell-surface TNF receptors.

– It is effective for the treatment of a number of forms of inflammatory arthritis and other conditions, including RA, psoriatic arthritis, and ankylosing spondylitis.

– Administered once or twice weekly via subcutaneous injection.

TNF Inhibitors

2. Infliximab: – Infliximab is a chimeric monoclonal antibody to TNF α. The

term “chimeric” refers to the use of both murine and human components of the drug.

– It is used with methotrexate in the management of moderate to severe, active rheumatoid arthritis.

– Administered via intravenous infusion approximately every six weeks once a steady state has been achieved.

Other TNF Inhibitors

AdalimumabcertolizumabGolimumab

IL-Inhibitors

• Anakinra:– Anakinra, a recombinant human IL-1Ra.– Significantly less potent than TNF inhibitors in most

patients.– NOT recommended in a combination regimen with a

TNF inhibitor because of an increased frequency of serious adverse events, including serious infections

B-Cell Inhibitors• Rituximab:

– It is a chimeric monoclonal antibody that binds specifically to the CD20 antigen.

– Used mainly for treatment of non-Hodgkin's lymphomas and CML.

– In the treatment of rheumatoid arthritis, rituximab is given in a dose of 1 g, for 2 doses; the infusions are separated by 2 weeks. It is given with methotrexate, and intravenous corticosteroids are recommended before each infusion to reduce the incidence and severity of infusion reactions.

Selective co-stimulation modulators

• Abatacept:– Abatacept, a fusion protein, is a co-stimulation blocker.

– It has been approved by the United States Food and Drug Administration for the treatment of patients with moderately to severely active RA who have had an inadequate response to one or more disease modifying antirheumatic drugs (DMARDs)

or tumor necrosis factor (TNF) inhibitors.

Side Effects

APPROACH TO THE MANAGEMENT of Ra

Establish Early Diagnosis

Clinical

EULAR

Start DMARD

(Methotrexate)Monitor response

Continue with MTX(7.5MG/Wk upto 17.5-20MG/WK

Comb DMARDS

Add Biologics

NOYES