New data have prompted an update of a widely cited consensus statement on biologic agents for rheumatic arthritis, psoriatic arthritis, ankylosing spondylitis, and other rheumatic diseases, according to Dr. Daniel E. Furst and the other members of the international expert panel that revised the document.
The addition of biologics to the treatment options for rheumatic diseases has greatly improved outcomes, and research continues on the best use of these agents. The panel, made up of rheumatologists from universities in Europe, North America, South America, Australia, and Asia, cited new findings encompassing tumor necrosis factor (TNF)–alpha blocking agents, abatacept, rituximab, tocilizumab, and interleukin 1 (IL1) receptor antagonists.
TNF-Alpha Blockers
The TNF-alpha blockers infliximab, adalimumab, and etanercept are most often used for rheumatoid arthritis in combination with other disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. New evidence has indicated that combining methotrexate with a TNF-alpha inhibitor is more effective for RA than is a combination of DMARDs without a TNF-alpha blocker, according to the new consensus statement (Ann. Rheum. Dis. 2010;69[suppl 1]:i2–29).
The dose of TNF-alpha blockers can be lowered during times of RA remission or low disease activity without loss of effectiveness, according to the update. Also, one TNF-alpha blocker may be substituted for another that has stopped working for RA, according to one randomized, controlled trial and several retrospective, observational studies cited by Dr. Furst, the Carl M. Pearson professor of medicine at the David Geffen School of Medicine, of the University of California, Los Angeles, and his coauthors.
In patients with psoriatic arthritis, all of the approved TNF-alpha blockers have been shown to be equally effective. Golimumab was approved for this indication since the last consensus statement on biologic agents was released.
In ankylosing spondylitis, regular infliximab therapy was more effective than “on demand” therapy. Adding methotrexate to infliximab did not increase effectiveness of treatment, the update noted.
Cardiovascular events decreased in patients taking TNF-alpha blockers, according to the results of several new studies. Although previous studies found a link between TNF-alpha blockers and a higher risk of solid tumors, subsequent analyses of the same data found no link.
Caution and repeat testing should be used when these agents are used in populations with a high prevalence of tuberculosis. Some evidence suggests that TNF-alpha antagonist therapy can be reinitiated following TB treatment.
TNF-alpha blockers have been associated with the development or exacerbation of psoriasis, but prescribing a different TNF-alpha blocker may resolve the problem, according to the update.
Abatacept
New evidence suggests that in methotrexate-naive patients with early RA, initiating treatment with methotrexate plus abatacept is more effective than using methotrexate plus placebo, Dr. Furst and his colleagues wrote.
Autoimmune disease incidence was not increased with abatacept, according to the clinical trial database for the drug.
Recent evidence supports earlier findings that abatacept use decreased response to vaccinations for influenza, pneumococcal, and tetanus infections, so the previous recommendation that live vaccines not be used within 3 months of abatacept treatment remains valid.
Rituximab
Clinical trials have shown that rituximab can slow radiographic progression of rheumatoid arthritis for up to 2 years. Also, after one or more TNF-alpha blockers have been ineffective, rituximab has been shown to be more effective than another TNF-alpha inhibitor, according to the update on biologic agents.
Rituximab is contraindicated in patients with hepatitis B infection, as fatal HBV reactivation has been reported with its use in non-Hodgkin's lymphoma patients. Risk of other serious infections did not increase with repeated courses of the drug, and did not increase in patients who received another biologic after rituximab.
Like abatacept, rituximab decreased the immune response to pneumococcal vaccine, but unlike abatacept, it did not decrease response to tetanus vaccine. However, live vaccines should be given before rituximab, the update authors said.
Tocilizumab
Recent studies showed that tocilizumab, used alone or in combination with methotrexate for rheumatoid arthritis in patients with an unsatisfactory response to DMARDs or TNF-alpha blockers, did not increase rates of cardiovascular events or cerebrovascular accidents.
However, the update said that tocilizumab has been linked with cases of peritonitis, lower GI perforation, fistulae, and intra-abdominal abscess. Hepatic failure and liver damage have not been reported, but liver function should be monitored because of increased bilirubin levels with this drug.
IL1 Blockers
Anakinra is the only IL1 blocker approved for the treatment of RA in the United States. Rilonacept has been approved for cryopyrin-associated periodic syndromes, but is clinically effective in only a few patients with the autoinflammatory syndrome.