NSAIDS
Provide some symptomatic relief
Do not prevent erosion
Do not alter disease progression
Not appropriate for monotherapy. Should only used conjunction with DMARDs
All have equivalent efficacy
Celecoxib: Selective COX 2 inhibitor
As effective as NSAID treating RA, but less upper GI tract adverse effect (obstruction, perforation,
hemorrhage, ulceration)
Long term use without ASPIRIN
Inc risk of Cardiovascular event
Adverse Effect: GI
NSAIDS
Inhibit COX 1 and COX 2
Gastric ulceration, perforation, GI hemorrhage
Low: 1:6000
Inc:
Long term use Higher NSAIDs dose
Present of RA Over 70
Hx of PUD or alcoholism
Concomitant corticosteriod or anticoagulant
Causing lower intestinal tract perforation or aggravating inflammatory bowel disease
Indomethacin & Piroxicam
Inhibit COX 1 in stomach
Higher risk of GI bleeding
Prevention:
Add proton pump inhibitor (Omeprazole 20mg orally daily) OR misoprostol
Expensive
Reserve for px with high risk of NSAIDs induce GI toxity
Adverse Effect: Renal
All NSAIDS: Aspirin and COX 2 inhibitors
Renal toxicity
Interstitial nephritis Nephrotic syndrome
Prerenal azotemia Aggravation of hypertension
Risk
Age over 60 Hx of renal disease
CHG Ascites
Diuretic use
Adverse Effects: Platelets Effects
Interfere with platelet function and prolong bleeding time
Effect on bleeding time resolves as drug clear
Except: Aspirin
Aspirin: irreversible inhibit platelet funciton
Except: no acetylated calculates and COX 2 inhibitor
Do not inhibit platelet function
Do not inc risk of bleeding
Inc risk of MI & stroke when use in high dose for prolong period of time
Combination of low dose aspirin & COX 2 inhibitor
GI adv ??????????
CHANGE NEW NSAID IF PREVIOUS PRESCRIBE NOT EFFECTIVE IN PX
Corticosteriods
Low dose corticosteroid (oral prednisone 5-10 mg daily)
Promt anti inflammatory in RA
Slow rate of bone destruction
Multiple side effect limit their long term use
Take measure to prevent osteoporosis
Purposes
Acute disable episodes
Facilitate other treatment measures (physical therapy)
Manage serious extra-articular manifestion (periditis, necrotizing scleritis)
Active disease persists despite tx with DMARDS
No more than 10 mg per day
5-7.5 mg daily
Discontinue gradually
Intra-articular Corticosteriod: TRIAMCINOLONE 10-40 mg
One or 2 joints involved
Given for symptomatic relief
No more than 4X per year
Synthetic DMARDS
Methotrexate
Initial choice of DMARDS treating RA
Well tolerated
Beneficial effect in 2-6 weeks
Initial doses: 7.5 mg/once weekly oral
Tolerate & not response in 1 month
Inc to 15 mg oral one per week
Max 25 mg/week
SE:
Gastric irritation & stomatitis
Life threatening interstitial pneumonitis
Rare
Stop med and start corticosteriods
Hepatotoxicity with fibrous & Cirrhosis
Very rare
After 5 y of methotrexate therapy
Inc risk in diabetes, obesity, renal disease
Heavy alcholism
Reduce by
Daily dose of folate (1mg)
Weekly dose of leucovorin calcium (2.5 to 5 mg 24 after dose
of methotrexate)
Inc risk of B cell lymphomas
Liver function test, CBC, Serum creatinine & albumin
Every 4-8 weeks
Combination: Methotrexate & Folate antagonist (trimethoprim-sulfamethoxazole)
Caution: pancytopenia
Probenecid
Avoid: inc methotrexate drug levels and toxicity
Sulfasalazine
2nd line agent for RA
Initial: .5 g 2X daily oral
Inc each week by . 5 g until px improve or reach 3 g
SE:
Neutrogena & thrombocytopenia
Hemolysis in G6PD px
Check G6PD level before given med
CBC
Every 2-4 weeks for 1st 3 months, then every 3 month
Leflunomide
Pyramiding syn inhibitor
Single dose daily of 20 mg
SE:
Diarrhea Rash Reversible alopecia Hepatotocity
Dramatic weigh loss ( some px)
Carcinogenic teratogenic
Contradication
Premenopause women & men want to have children
Antimalarial
Hydroxychloroquine Sulfate
Most often used for RA
Reserve for mild disease
Only 25-50% px response
Effective only after 3-6 month of therapy
Low toxicity at dose of 200-400 mg/d oral
SE
Pigmentary retinitis causing visual loss: rare
Optha exam ever 12 month if med use long term
Neuropathies
Myopathy of skeletal and cardiac muscle
Improve with drug withdraw.
Combination: Hydroxychloroquine Sulfate + methotrexate or sulfasalazine
Minocycline
Reserve for early, mild
Efficacy is modest
Work during 1st year of RA
200mg/daily oral
SE
Dizziness (10%)
Biologic DMARDS
Tumor Necrosis Factor Inhibitors
Fulfill the aim of target therapy for RA
Use for px do not response to methotrexate
Add to methotrexate for poor prognosis px
Reduce need for prednisone
SE:
Inc risk of infection: TB
Screen for latent TB recommended before TNF blocker
Stop TNF blocker if px have fever or sign of infection
Demyelinating neurologic complication: Resemble multiple sclerosis
Inc morbidity in CHF
Caution in CHF px
$$$$$$: 10,000 per year
3:
Etanercept Infliximab Adalimumab
Etanercept
Soluable recombinant TNF receptor: Fc fusion protein
Dose: 25 mg SQ 2X weekly or 50 mg once per week
Infliximab
Chimeric monoclonal antibody
Dose: 3-10 mg/kg IV initially
Repeat after: 2, 6, 10, 14 weeks
Adalimumab
Recombinant monoclonal antibody bind to TNF receptor
Dose: 40 mg SQ every other weeks
Common
Produce substantial improvement
Very well tolerated
Etanercept & adalimumab
Minor injection site irritation
Abatacept
Recombinant protein fusing fragment of FC domain of human IgG with extra cellular
domain of T cell inhibitory molecules (CTLA4)
Treat px not response to methotrexate and TNF inhibitor
Rituximab
Humanized mouse monoclonal antibody that delete B cell
Combine with methotrexate
Refractroy to tx with TNF inhibitor
DMARD Combination
Greater efficacy
Most common
Methotrexate + one of TNF inhibitor
Concern: inc risk of serious infection & malignancy 2X-3X
Reserve for px not response to adequately to individual agent