Rheumatoid Arthritis

• Common inflammatory arthritis.

• Chronic disease with of exacerbations and remission

• Prevalence
Europe approximately 0.8–1.0%
South-east Asia (0.4%)

• Female-to-male Ratio of 3 : 1
 Genetically
predisposed
Environmental Infections
(HLA-DR)Smoking
Components

RA
DRUG THERAPY IN RHEUMATOID ARTHRITIS
Aims of t/t
• Reduce inflammation
• Relieve pain
• Prevent or delay joint damage
• Reduce disability
• Last two decades have changed the t/t of RA

• Emergence of methotrexate as the (DMARD) of first

choice for the treatment of early RA

• Development of novel highly efficacious biologicals

• Proven superiority of combination DMARD regimens

over methotrexate alone
 DRUGS
• ACETAMINOPHIN & NSAIDs

• COTICOSTEROIDS

• DMARDs
Non Biologics
Biologics

• IMMUNOSUPPRESSIVES
NSAIDs

• Core t/t modality in early days

• Adjunctive agents: Currently

• Anti inflammatory & Analgesics

• Block COX1 & COX2

• Chronic use : Gastritis/PUD/Nephrotoxicity

• Paracetamol 1g QID may be safer alternative as it
acts by inhibiting PG synthesis in brain with very
little effect on peripheral PG synthesis.
Glucocorticoids

• Anti inflammatory and immunosuppression

• Promote apoptosis

• Inhibit activation of many proinflammatory

pathways
GLUCOCORTICOIDs

Burst High Dose Chronic low dose Intraarticular

Acute Disease Flares To Control Disease Activity Triamcinolone Acetonide
in Inadequate Response To
DMARD Therapy
Severe Extraarticular One/ Few Actively Inflamed
Manifestations : ILD Joints
Prednisolone 30 mg Prednisolone 5 mg Methylpred : 40-80 mg
DMARDS
• Slow/Prevent structural progression of RA.

• Conventional DMARDs are

hydroxychloroquine, sulfasalazine,
methotrexate, and leflunomide.

• They exhibit a delayed onset of action of ~6–

12 weeks
 DMARDS Classifications
NON BIOLOGICS BIOLOGICS
METHOTREXATE ETANERCEPT
SULFASALAZINE INFLIXIMAB
HYDROXYCHLOROQUINE ADALIMUMAB
AZATHIOPRINE CERTOLIZUMAB
LEFLUNOMIDE GOLIMUMAB
CYCLOSPORINE
GOLD SALT; D PENICILLAMINE
METHOTREXATE

• Approved for the treatment of RA in 1988

• First choice for the treatment

• Anchor drug for combination therapies.

• Mtx inhibits folic acid reductase, preventing formation of tetrahydrofolate,
which is necessary for DNA synthesis in
leucocytes and other cells.

• It is given orally in a starting dose of 10–15 mg weekly and escalated in 2.5

mg increments every 2–4 weeks to a maximum of 25 mg weekly until benefit
or toxicity occurs.

• Folic acid (5 mg/week) reduces adverse effects without

impairing efficacy
LEFLUNOMIDE
• An inhibitor of pyrimidine synthesis

• Effective as mono-therapy or in combination with

methotrexate and other DMARDs

A/E :
• Hepatotoxicity, HTN, Hirsutism

• Caution : Pregnancy
SULFASALAZINE
• Can be used alone and or combination with
MTX and another DMARD.

• Mechanism of action is incompletely

understood

• RCTs : Reduce radiographic progression.

HYDROXYCHLOROQUINE
• Not considered to be a true DMARD

• Do not delay radio-graphic progression.

• Non used as monotherapy rather as adjunctive

• Safe during pregnancy.

• Minocycline, gold salts, penicillamine,
azathioprine, and cyclosporine have all been used
for the treatment of RA with varying degrees of
success; however, they are used sparingly now
due to their inconsistent clinical efficacy or
unfavorable toxicity profile
 BIOLOGICS : ANTI TNF THERAPY

• Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that plays an

important role in joint inflammation and
contributes to joint destruction.

• The inhibition of TNF improves the clinical manifestations and reduces

radiographic progression.

• 5 approved biologics targeting TNF :

infliximab (INF), etanercept (ETN), adalimumab (ADA),
certolizumab (CMZ) and golimumab (GLM
IV every 4-8 weeks
S/c
• Anti-TNF therapy : C/I

Active Infections
Untreated Tuberculosis
 Indwelling Catheters,
Severe Heart Failure And
Multiple Sclerosis,
 JANUS KINASE INHIBITORS
TOFACITINIB

• Inhibiting JAK enzymes : Intracellular signal: key

role in transduction of pro inflammatory
cytokines

• They are indicated for patients with RA

who have responded inadequately to standard
DMARDs and provide an alternative to biologic
treatments
• Two JAK inhibitors are currently available:

• Tofacitinib, dose of 5 mg twice daily

• Baricitinib, dose of 2–4 mg once daily.

• The main A/E

Opportunistic Infections
Hepatotoxicity
 Cytopenias.
 ABATACEPT
• Fusion protein that inhibits T cell activation by
binding to CD80/CD86.

• Abatacept reduces disease activity in MTx

inadequate rensposive patients.

• The main adverse effect is an increased risk of

infections
TOCILIZUMAB
• Tocilizumab is a monoclonal antibody to the IL-6 receptor.

• It is indicated in patients with RA who have not responded adequately to first-line therapy or to
TNF inhibitors.

• Adverse effects include

Leucopenia,
 Abnormal Lfts,
Hypercholesterolaemia,
Hypersensitivity Reactions
Diverticulitis
RITUXIMAB

• Rituximab is an antibody directed against the CD20 receptor, which is

expressed on B lymphocytes and immature plasma cells.

• It causes profound B-cell lymphopenia

• Rituximab is indicated in patients with RA who have not responded

adequately to first-line therapy but is typically employed as a
third-line treatment when TNF inhibitors have been ineffective.
Adverse effects include

 Hypogammaglobulinaemia
 Infusion Reactions
 Increased Risk Of Infections
 Progressive Multifocal Leucoencephalopathy
In Summary
Thank you