Claire Bombardier, Loren Laine, et al
Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis.
New Eng J Med., Vol.343, November 23, 2000, pg. 1520-1528.
Clinical upper gastrointestinal events occur in 2-4 percent of patients who take NSAIDs. Authors have compared rofecoxib (selective inhibitor of cyclooxygenase-2) and naproxen (nonselective NSAID), as regards clinically important upper GI events in patients with rheumatoid arthritis.
Authors assigned 8076 patients (who were receiving long term glucocorticoid therapy for rheumatoid arthritis) to receive either 50mg rofecoxib daily or naproxen 500mg twice daily. Primary end point was confirmed clinical upper GI events (symptomatic gastroduodenal ulcers, perforation or obstruction, and upper GI bleeding).
It is concluded that in patients with rheumatoid arthritis, treatment with Rofecoxib is associated with significantly fewer clinically important upper GI events as compared to treatment with naproxen.
Joan M Bathon, Richard W.Martin et al
A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis.
New Eng Jr.Med. Vol.343, November 30, 2000, pg.1586-1593
Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is not known.
Authors treated 632 patients with early rheumatoid arthritis with either twice weekly subcutaneous etanercept (10 or 25mg) or weekly oral methotrexate (mean, 19mg/week) for 12 months. Clinical improvement was defined as percent improvement in disease activity according to criteria of American College of Rheumatology.
As compared with oral methotrexate, etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis.
Peter E Lipsky, Desiree M.F.M., et al
Infliximab and Methotrexate in Treatment of Rheumatoid Arthritis.
New Eng J Med. Vol.343, November 30, 2000, pg.1594-1602
Tumour necrosis factor a (TNF a) has a central role in pathogenesis of rheumatoid arthritis, as seen by clinical benefit of TNF a -neutralizing therapy – with either a TNF a – type II receptor – IgG1 fusion protein (etanercept) or a chimeric (human and mouse) monoclonal antibody against TNF a (infliximab).
Authors treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy, with placebo or infliximab (IV doses of 3 or 10 mg/kg body weight) every 4 or 8 weeks in combination with oral methotrexate for 54 weeks.
In patients with persistently active rheumatoid arthritis despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted progression of joint damage.
Biologic therapy for rheumatoid arthritis
Products devised by the biotechnology industry for treatment of rheumatoid arthritis have now been introduced. Products inhibiting TNF a have been introduced and other biologic therapies are expected to follow. The cytokine TNF a has a major role in inflammation and bone resorption, In addition to rheumatoid arthritis etanercept has been approved for polyarticular juvenile rheumatoid arthritis, and infliximab for use in patients with active Crohns disease and fistulae due to Crohns disease.
TNF a inhibitors should be used as early as possible in all rheumatoid arthritis patients, but at present the cost is prohibitive. Cost savings of early therapy will be reduction in need for long term care for chronic disease and extent of disability caused by joint damage.
TNF a inhibitors have few side effects. Most common are reactions at the injection site (for etanercept) and hypersensitivity reactions (for infliximab) and minor upper respiratory tract infections. Serious life-threatening infections have also occurred. Several cases of pancytopenia and demyelinating syndromes in a few patients treated with etanercept have been reported (inhibition of TNF a worsens multiple sclerosis). These effects serve as a reminder that our understanding of the risks of inhibiting TNF a remains incomplete.