Systemic GC therapy – Provide effective symptomatic therapy in patients with RA – Low dose PREDNISONE (<7.5 mg/dl) Useful additive therapy to control symptoms May retard the progression of bone erosions Initial course of low dose GC may have a long term protective effect against bone damage LOW DOSE GC + DMARD therapy (i.e. Methotrexate) can be beneficial in controlling sins and symptoms rapidly and affording long term retardation of bone erosion Source: Harrison’s Principles of Internal Medicine 17 th ed.
DMARDS (Disease-Modifying Anti-rheumatic Drugs) 3 rd line of therapy
Slows down the progression of joint destruction Slow acting because it may take 6 weeks to 6 months for it to become evident Methotrexate, azathioprine, penicillamine, hydroxychloroquine and chloroquine, organic gold compounds, sulfasalazine
Methotrexate DMARD of FIRST choice to treat RA Individuals with RF for development of bone erosions or persistent synovitis or >3months
MOA: – Inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase and thymidylate synthetase, with secondary effects on polymorphonuclear chemotaxis
Pharmacokinetics – 70% absorbed after oral administration – Metabolized to a less active hydroxylated metabolite and both the parent compound and the metabolite are polyglutamated within cells where they stay for prolonged periods – Half-life: 6-9 hours – Increased in the presence of hydroxychloroquine – Excreted primarily in the urine
Indications – Dosing regimen: 15-25 mg weekly, 30 or 35 mg weekly has an increased effect – Decreases the rate of appearance of new erosions – Juvenile chronic arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, Wegener’s granulomatosis, giant cell arteritis, SLE and vasculitis Maximal improvement is observed after 6 months of therapy
Adverse Effects – Nausea and mucosal ulcers – most common – GI upset – Progressive dose-related hepatotoxicity (enzyme elevation) occurs frequently – Contraindicated in pregnancy Source: Basic and Clinical Pharmacology 10 th edition, 2007 by Katzung
MOA: – Costimulation modulator that inhibits the activation of T cells.
Pharmacokinetics – IV infusion – 3 doses (day 0, week 2 and week 4) initially – Followed by monthly infusions – Dose is based on body weight <60kg – 500mg 60-100kg – 750mg >100kg – 1000g – Half-life: 13-16 days – Coadministration with methotrexate, NSAIDs and corticosteroids does not influence clearance of abatacept
Indications – Can be used as monotherapy or in combination with other DMARDs in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to DMARDs or TNF antagonists. – Reduces the clinical signs and symptoms of rhematoid arthritis, slows the progression of damage to the joints, and improves the physical function of patients
Adverse Effects – Increased risk of upper respiratory tract – concomitant use with TNF antagonists is NOT recommended due to increased risk of infection Source: Basic and Clinical Pharmacology 10 th edition, 2007 by Katzung
Azathioprine, leflunomide, cyclosporine and cyclophosphamide Effective in the treatment of RA and exerts therapeutic effects similar to DMARDs DMARDs > immunosuppressive agents Increase toxicities Reserved for patients who have failed DMARDs and biologics therapy Source: Harrison’s Principles of Internal Medicine 17 th ed.