This presentation contains information regarding Rheumatoid arthritis (RA) and its treatment medications.

1. Presented By -
Payal Sharad Rakshe.

2.  Introduction:
 Rheumatoid arthritis (RA) is an autoimmune disease in which there is joint
inflammation, synovial proliferation and destruction of articular cartilage.
 Immune complexes composed of IgM activate complement and release cytokines
(mainly TNF α and IL-1) which are chemotactic for neutrophils.
 These inflammatory cells secrets lysosomal enzymes which damage cartilage and erode
bone, while PGs produced in the process cause vasodilation and pain.
 RA is a chronic progressive, crippling disorder with a waxing and waning course.
 Multiple small joints of hands and feet are preferentially affected; deformities are
produced as the disease progresses.

3. Cytokine release, chemotaxis, proliferation of immune cells
⬇️
Activation of T-cell and APC
⬇️
Release of IL-1,IL-4,IL-10, IL-11, IL-13,TNF-alpha
⬇️
Activation of macrophages, fibroblasts, chondrocytes and osteoclasts, proliferation of
synovial cell
⬇️
Arthritic condition
 Pathophysiology :

4.  Antirheumatic Drugs :
 These are drugs which (except corticosteroids), can suppress the rheumatoid process,
bring about a remission and retard disease progression, but do not have nonspecific anti-
inflammatory or analgesic action.
 They are used in rheumatoid arthritis (RA) in addition to NSAIDs, and are referred to as
disease modifying antirheumatic drugs (DMARDs) or slow acting antirheumatic drugs
(SAARDs).
 They are used in rheumatoid arthritis (RA) in addition to NSAIDs, and are referred to as
disease modifying antirheumatic drugs (DMARDs) or slow acting antirheumatic drugs
(SAARDs).
 The onset of benefit with DMARDs takes a few months of regular treatment, and
relapses occur at least a few months after cessation of therapy.
 The onset of benefit with DMARDs takes a few months of regular treatment, and
relapses occur at least a few months after cessation of therapy.

5.  Symptoms :
 Weight loss
 Fatigue
 Swelling
 Stiffness of joint
 Joint tenderness
 Numbness and tingling
 Joint redness
 Pain in joints

6.  Classification :

7. I) DMARDs :
A) Nonbiological drugs :
a) Immunosuppressant –
i) Methotrexate -(Mtx)
This dihydrofolate reductase inhibitor has prominent Immunosuppressant and anti-
inflammatory property.
MOA -
Act by inhibiting dihydrofolate reductase leading to inhibition of :
 Cytokine production

8.  Chemotaxis
 Cell mediated immune reaction
 Proliferation of immune cells
Uses –
① Methotrexate treats cancer by slowing the growth of cancer cells.
② Methotrexate treats psoriasis by slowing the growth of skin cells to stop scales from
forming.
③ Methotrexate may treat rheumatoid arthritis by decreasing the activity of the immune
system.

9. ii) Azathioprine –
MOA –
This purine synthase inhibitor acts after getting converting to 6-mercaptopurine by the enzyme
thiopurine methyl transferase(TPMT)
⬇️
Suppressed cell mediated immunity
⬇️
Selectively affect differentiation and function of T-cell and natural killer cells
⬇️
Suppresses inflammation and slow the progression of RA
Uses -
① Azathioprine is used to prevent organ rejection in people who have received a kidney
transplant.
② Azathioprine is also used to treat rheumatoid arthritis.

10. Contraindication -
① Pregnancy
② Breast feeding
③ Liver disease
④ Active infection
⑤ Leucopenia
⑥ Peptic ulcer
ADR -
① Oral ulceration
② Gastrointestinal upset
③ Dose dependent progressive liver damage
leading to cirrhosis
④ Predisposed to chest infection

11. b) Other immunomodulatory –
i) Sulfasalazine -
MOA –
Sulphapyridine split off in the colon by bacterial action and gets absorbed
⬇️
Suppressed generation of superoxide radicals and cytokine elaboration
⬇️
Relieve symptoms of RA

12. ii)Leflunomide –
Potent immunomodulator
MOA –
Leflunomide is rapidly converted in the active metabolites
⬇️
Inhibits dihydro-orotate dehydrogenase
⬇️
Inhibits pyrimidine synthesis which depressed cell proliferation
⬇️
Depressed antibody production by beta cells.

13. Contraindication –
① Pregnant women
② Active infection
③ Liver disease
④ Lactating mother
ADR –
① Diarrhea
② Headache
③ Nausea
④ Rashes
⑤ Thrombocytopenia
⑥ Leucopenia
⑦ Increased chance of chest infection

14. B) Biological agents :
a) TNF-α inhibitors –
MOA –
 Binding to TNF-α cytokines and neutralize it
 TNF-α not available to bind to TNF- receptors present on T-cells, Macrophages
 Function of T-cells and macrophages suppressed
ADR -
i)Etanercept -
Pain, Redness, itching and swelling at injection site
ii) Infliximab -
Acute reaction (fever, bronchospasm), worsening of CHF.

15. b) Other biologicals –
i) Abatacept –
 Binding to CD80 and CD86 molecules
 Blocked the second signal for
Co-stimulation of T-cells.
Approved for moderate to severe active
RA not responding to Mtx.
Not to be combined with TNF-alpha
inhibitors.
Uses -
 This medication is used to treat rheumatoid arthritis, a condition in which the body's own
defense system

16. (immune system) attack healthy tissue.
 Abatacept works by weakening your immune system.
ii) Rituximab
Chimerized monoclonal Antibody
MOA -
 Binding to CD20 beta cell antigen
 Promotes apoptosis
Approved for active RA not responding to Mtx+TNF-α inhibitors.
ADR -
Infusion reaction, late onset neutropenia, depletion of beta lymphocytes, skin reactions.

17. II) Adjuvant drugs –
Prednisolone-
MOA –
 As a glucocorticoid, the lipophilic structure of prednisolone allows for easy passage
through the cell membrane where it then binds to its respective glucocorticoid receptor
(GCR) located in the cytoplasm.
 Upon binding, formation of the GC/GCR complex causes dissociation of chaperone
proteins from the glucocorticoid receptor enabling the GC/GCR complex to translocate
inside the nucleus.
 This process occurs within 20 minutes of binding. Once inside the nucleus, the
homodimer GC/GCR complex binds to specific DNA binding-sites known as
glucocorticoid response elements (GREs) resulting in gene expression or inhibition.
 Complex binding to positive GREs leads to synthesis of anti-inflammatory proteins while
binding to negative GREs blocks the transcription of inflammatory genes.

18. Contraindication -
Systemic infection, hypersensitivity to components.
ADR -
 Nausea
 vomiting
 loss of appetite
 heartburn
 trouble sleeping
 increased sweating, or acne may occur.
Uses -
 It helps by reducing inflammation.