Treatment of RA

Question 1

What are goals ?

Answer 1

1. reduce pain + DA - ideally remission ASAP
2. protect articular structure + func
3. control systemic complications
4. improve QOL

Question 2

DMARDs

Answer 2

• 1/more initiated
• modify underlying cause + symptomatic relief
• trad/syntethic + biologic
• synthetic dmards - MXT, Chloroquine sulphate, leflunomide, sulphasalazine
• take weeks - months to work
  AVOID COMBO TREATMENT BIOLOGIC DMARDS ESTABLISHED RA > 6M due to increased risk of infec

Question 3

Non-pharmacological therapy

Answer 3

1. occupational + physical therapy - preserve jt func , extend jt rom , streghten jts + muscles
2. joint deformities - minimize disability
3. counsel stress management

Question 4

Bridge therapy / symptomatic relief

Answer 4

1. NSAIDs
   - analgesic, anti-inflamm = joitn pain + swelling
   - depends on CV risk, GI ADR + adherence
2. Glucocortioids
   - low-dose G < prednisons 1-mg/day
   - reduce inflamm = inhibit cytokines + inflamm mediators
   - duration < 3m
   > prednisone 2/5mg/day lead to osteoperosis / bone loss
   - intraarticular adm into joints
   - cause cushing syndrome, peptic ulcer, HPT, weight gain, infection, mood changes, cataracts, dyslipidemia, hyperglyceamia

Question 5

Methotrexate = MTX

Answer 5

• synthetic
• monotherapy/ combo
• anti-inflamm
• inhibits DHF-R - inhibit purines + thymidylic acid + inhibit production certain cytokines
• ONCE week dosing not daily - myelosuppression - infection + bleeding
• swithc to MTX sc -off-lable - intolerant to git s/e
  ++ folic acid - reduce folate depleting rxns - stomatitis, d, alopecia, myelopsuppression, elvated LFT

Question 6

chloroquine

Answer 6

• MOA unkown
• well tolerated
• slow OA - given atleast 6m before treatment failure
  = option if patient c/i to other DMARDs
  = not associated renal, hepatic/ BM suppression

Question 7

sulfasalazine

Answer 7

• MOA unknown
• minimize nausea + abdominal discomfort = start low doses + titrate slowly
• sulfa allergy - NOT be given

Question 8

Leflunomide

Answer 8

• inhibits dihydroorotate DH - enzyme in mitochondria supplies T- lympoh with cytokine stimulation
• inhibits T-lymp + halt cell cycle
• similar MTX/ sulfa
• extended t1/2 - begin with LD
• • MTX = hepatoxicity
• abrupt discontinuation - adm cholestyramine - accelerate removal lef from body

Question 9

Biologic DMARDs

Answer 9

• failed treatment synthetic DMARDS
• added monotherapy
• replace ineffective synthetic DMARD
• considered intiial therpay

biosimilars and ref product

• used caution ‘
• lymphorpoliferative disease
  hepatitis
  history malig
  HF

Question 10

TNF antagonist

Etanercept

Answer 10

• recombinant form human T-recep
• bind to soluble TNF = prevent binding to TNF-R
• alone / combo synthetic

Question 11

TNF antang

Adaliumumab

Answer 11

• recombinant human IgG1 monoclonal antibody
• specific human TNF
• binds soluble + bound TNF-alpha
• adm with MTX / other Dmards

Question 12

TNF antag

Infliximab

Answer 12

• chimeric IgG1 monoclonal antibody
• binds soluble + bound TNF-alpha
• given with MTX = suppress antibody production against nouse-derived portion mol
• infusion related rxts - rash urticaria etc
  1. discontinue infusion
  2. slow infusion rate
  3. adm corticosteroid / antihistamine

Question 13

TNF antag

Golimumab

Answer 13

• human monoclonal antibody
• binds membrane-bound + soluble TNF
• given MTX = moderate - severe RA
• once-monthly SC/ every other month IV dosing

Question 14

Abatacept

co-stimulation modulator

Answer 14

• interfer T cell signaling
• block t-cell activation
• cause anergy - lack response to antigen
• monotherapy / combo synthetic

Question 15

Rituximab

generically engineered chimeric anti-CD20 monoclonal antiboy

Answer 15

• B-lympho depletion in BM + synovial tissue
• patients moderate-severe RA
  -history inadequate response 1/more TNF antagonists
• RF +favour rit
  ADR - fatal infusion rxns , severe mucocutaneous rxns, heaptitis B reactivation, progressive multifocal leukoencephalopathy

Question 16

Tocilizumab

anti-L6 -R monoclonal antibody

Answer 16

approved for moderate-severe Ra

HIGH LEVELS IL-6 inicate joint damae + disease progression

Question 17

select DMARD

Answer 17

• based precriber comfort level
• risk of infect - use of TNF antag - history of TB exposure - screen for TB
• check immunization status before therapy - reduce bodys ability to mount response to pathogen/ vaccine
• killed + recombinant vaccines - adm prior to intiation

Question 18

feritlity , pregnancy and foetal development

Answer 18

• counselled on risks
• present signs RA postpartum
• DMARDs teratogens
• consider:
  1. low-dose corticosteroid
  2. Nsaids
  3. chloroquine
  4. Sulfasalazine
  5. certain biologic DMARDS
  MTX - spontaneosu abortion, foetal myelosuppresion , limb defects, CNS abnormallities - discontinue 3 m prior conception

TNF antag - safe in 1st trime
Etanercept - continued throughout pregnancy
Rituximab - disonctinue 1 year prior conception
Abatacept - discontinue 10w prior to planend conception
Toclixiumab unknown
males counselled risks of fertilitiy and potential harm to foteus