Presentation
topic
TRADITIONAL DISEASE –
MODIFYING
ANTIRHEUMATIC DRUGS
D M A R D ’S
RHEUMATOID ARTHRITIS
• A long lasting autoimmune disorder.
• Primarily affects joints.
• Result in warm, swollen and painful joints.
• Wrist and hands are more commonly involved.
• Cause is not clear but believed to involve genetic and environmental
factors.
• Affects bone and cartilage
Rheumatoid arthritis
GOALS OF THERAPY
Relieve symptoms, including fatigue, pain, swelling, and stiffness
Prevent joint destruction, loss of joint function, deformity, disability, and
early death
Preserve quality of life
• Achieve clinical remission
DMARD’S
A category of unrelated drugs defined by their use in
rheumatoid arthritis
Also called Remission Inducing Drugs (RIDs) OR Slow Acting Anti Rheumatic Drugs
(SAARDs)
• Reduce symptoms of RA
• Decrease pain and inflammation, reduce or prevent joint damage, and preserve the
structure and function of the joints
• Its effect take 6weeks- 6months
• Slow acting as compared to NSAIDS
TRADITIONAL DMARDS
• Methotrexate
• Hydroxychloroquine
• Leflunomide
• Sulfasalazin
• Glucocorticoids
METHOTREXATE
Methotrexate is a folic acid antagonist with cytotoxic and
immunosuppressant activity and potent antirheumatoid action.
It is a common first-choice drug.
• It has a more rapid onset of action than other DMARD’s
• Response to methotrexate usually occurs within 3 to 6 weeks of
starting treatment
• Dosage of methotrexate required for RA treatment are much lower than
those needed in cancer cancer chemotherapy
ADVERSE EFFECTS
• Mucosal ulceration
• Nausea
• Cytopenias
• Cirrhosis of liver
• Pneumonua
• Contraindicated in pregnancy, liver disease, peptic ulcer.
HYDROXYCHLOROQUINE
• It is used for early mild RA
• Its mechanism of action in autoimmune disorders is unknown and onset of effects
takes 6 weeks to 6 months
• Adverse effects
• Ocular toxicity
• CNS disturbance
• GI upset
• Skin discoloration
• Eruptions
LEFLUNOMIDE
• It is used as monotherapy in patients who have intolerance or contraindications to use
of methotrexate in RA
• Adverse effects
• Headache
• Diarrhea/nausea
• Weight loss
• Allergic reaction
• Alopecia
• Hypokalemia
SULFASALAZIN
• Sulfasalazin has recommended for use similar to leflunomide in the
treatment of RA
• It’s mechanism of action in treating RA is unclear
• Adverse effects
• Nausea
• Vomiting
• Anarexia
• Leukopenia
GLUCOCORTICOIDS
• These anti- inflammatory drugs that are commonly used in patients
with RA
• Glucocorticoids should always be used at the lowest dose and for the
shortest duration .
BIOLOGIC DISEASE –MODIFYING
ANTIRHEUMATIC DRUGS
Newer drugs that reduce RA inflammation in a more highly targeted
manner than the DMARDs. These are used when there is inadequate
response with the DMARDS
Biologics are made through biotechnology and target very specific
proteins or cells that are involved in the inflammatory process.
• Biologics have also been shown to help reduce the progression of joint
damage in RA.
BIOLOGIC DMARDS
• Are recombinant Proteins and monoclonal antibodies
• Derived from living organisms
• Hence called biological agents
• Classified as:
• TNF-a inhibitors
• Etanercept, Infliximab, Adalimumab
• Others biologicals
• Anakinra , Abatacept, Rituximab
BIOLOGIC RESPONSE MODIFIERS
• Adalimumab
• Certolizumab
• Etanercept
• Golimumab
• Infliximab
• Abatacept
• Rituximab
INFLIXIMAB
• Infliximab is a chimeric monoclonal antibody composed of human and murine regions
• The antibody binds specifically to human TNF-a and inhibit binding with it’s receptors
• This agent is not indicated for monotherapy
• Infliximab is administered as an IV infusion every 8 week, usually with mehtotrexate
• Adverse effects
• Fever
• Chills
• Pruritus
• Urticaria
RITUXIMAB
• Rituximab is a chimeric human monoclonal antibody directed against the CD20 antigen
• found on the surface of normal and malignant B lymphocytes
• Rituximab is administered as an IV infusion every 16 to 24 weeks
• Adverse effects
• Infusion reactions,
• late onset neutropenia,
• Depletion of B-lymphocytes,
• skin reactions
• Etanercept
• Binds tumor necrosis factor (TNF); is a recombinant form of TNF receptors
• Adalimumab
• Monoclonal antibody to TNF Infections
• Abatacept
• Recombinant fusion protein
• Binding to CD80 and CD86 molecule
• Signal for co-stimulation of T-cell blocked
OTHER DRUGS FOR RA
Janus kinases are intracellular enzymes that modulate immune cell
activity in response to the binding of inflammatory mediators to the cellular
membrane.
Tofacitinib is a synthetic small molecule that is an oral inhibitor of Janus
kinases. It is indicated for the treatment of moderate to severe established
RA in patients who have had an inadequate response or intolerance to
methotrexate
• Tofacitinib treatment may also increase the risk for new primary
malignancy and opportunistic infections.
• bDMARDs are expensive ,produce prominent adverse effects
• Used as reserve drugs for severe refractory disease
