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Rheumatoid Arthritis

 

  • 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, IL-6 and IL-1) which are chemotactic for neutrophils.
  • NSAIDs are the first line drugs and afford symptomatic relief in pain. Though mild/early cases are still mostly treated only with NSAIDs, the current recommendation is to add DMARDs as soon as the diagnosis of RA is confirmed.
  • More than one DMARD may be used concurrently; advanced cases may require 2 or 3 drugs together, because all DMARDs tend to lose effectiveness with time.

Disease Modifying Anti-Rheumatic Drugs:

 

IMMUNOSUPPRESSANTS

BIOLOGIC RESPONSE MODIFIERS

ADJUVANT CORTICOSTEROIDS

Methotrexate,
Azathioprine,
Cyclophosphamide
Cyclosporine
Cycloserine
Mycophenolate mofetil
Sulfasalazine
Chloroquine or Hydroxychloroquine
Leflunomide
Gold sod.thiomalate, Auranofin
d-Penicillamine

TNF-αïANTAGONIST: 
Etanercept, Infliximab, Adalimumab, Certolizumab, Golimumab
 
IL-1 ANTAGONIST: Anakinra
 
IL-6 ANTAGONIST: Tocilizumab
 
cd20 Mab: Rituximab
 
T Cell INHIBITOR: Abatacept
 
 

Prednisolone etc.

 

OLDER DMARD’s

  1. Hydroxychloroquine
    1. Suppress T lymphocytes        
    2. Anti-chemotactic            
    3. Concentrates in eye             
    4. Slowly acting
  2. Gold salts
    1. Aurothiomalate                       
    2. Aurothioglucose             
    3. Auranofin
      1. Anti-macrophages           
      2. Well absorbed after IM injection
      3. Long acting                     
      4. High efficacy                                   
      5. High toxicity

 

Side effects

  1. Rashes-MC                                               
  2. Nitritoid reactions (sweating, headache etc)             
  3. Neuropathy                             
  4. Nephrotic syndrome

 

  1. Infliximab
    (AIIMS Nov 08)
    1. Chimeric monoclonal antibody (IG1)                   
    2. TNF-alpha blocker
    3. Given IV infusion                                                     
    4. Long acting (half life=10 days)
    5. Uses
      1. Rheumatoid arthritis                      
      2. Crohn’s disease                              
      3. Psoriatic arthropathy

Side effects

  1. Infusion related side effects
  2. Anti-nuclear antibody (SLE can occur)
  3. Lymphomas (AIPG 2007, AIIMS 2010)
  4. Infections
    1. Reactivation of latent Tb (AIIMS 2009)
    2. Reactivation of latent hepatitis B
  1. Etanercept
    1. Recombinant fusion protein
      Given SC weekly/twice weekly 

Uses

  1. Rheumatoid arthritis                              
  2. JRA          
  3. Psoriasis               
  4. Psoriatic arthropathy
  5. Ankylosing spondylitis
    1. No value in Crohn disease

 

Side effects

  1. Infections                
  2. Lymphomas
  1. Abatacept  
  • Abatacept (which contains the endogenous ligand CTLA-4) binds to CD80 and 86, thereby inhibiting the binding to CD28 and preventing the activation of T cells.

 

P/K

  1. Given as IV infusion
  2. Long acting (half life=10 days)
  3. Use Refractory rheumatoid arthritis

Side effects

  1. Infections                
  2. Lymphomas                
  3. Not combined with other TNF alpha blockers
  1. Leflunomide
    1. Prodrug
    2. Inhibits dihydroorotate dehydrogenase
    3. Inhibits T cell proliferation/B cells antibody production
    4. Long acting (half life=20 days)
    5. Use Leflunomide is as effective as methotrexate in rheumatoid arthritis, including inhibition of bony damage.

Side effects      

  • Diarrhea         
  • Teratogenic
  1. Anakinra
    It is a interleukin 1 antagonist.
  2. Tocilizumab
    It is a interleukin 6 antagonist.

Combination Therapy Of Dmard’s:

When added to methotrexate background therapy, Cyclosporine, Chloroquine, Hydroxychloroquine, Leflunomide, Infliximab, Adalimumab, Rituximab, And Etanercept have all shown improved efficacy.

In contrast, Azathioprine, Auranofin, Or Sulfasalazine plus Methotrexate results in no additional therapeutic benefit.






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