A trend toward more aggressive treatment in patients just starting to develop rheumatoid arthritis is among the most important changes in treatment guidelines for the disease, according to updated American College of Rheumatology guidelines published today in the journal Arthritis Care & Research. The trend may proceed from emerging opinions that joint damage caused by RA is irreversible, and early, intensive therapy better preserves physical function, quality of life and capacity to work.
Researchers from the University of Alabama at Birmingham and UCLA led the effort by 18 institutions to update the ACR 2012 recommendations that guide physicians in the use of the two main RA treatment classes — disease-modifying anti-rheumatic drugs, or DMARDS, and biologic agents — for the first time since 2008.
More than 1 million Americans have RA — a chronic disease that causes pain and swelling in the lining of joints — and women represent 75 percent of patients. Physicians and patients must navigate a growing list of treatment choices, including DMARDs like hydroxycholorquine, methotrexate and sulfasalazine. Also important are biological agents, which include tumor necrosis factor-inhibitors etanercept and infliximab and non-TNF biologicals abatacept, tocilizumab and rituximab. New since 2008 are the biologics certolizumab pegol, golimumab and tocilizumab, which must also now be factored into treatment plans.
“With so many new advances in the treatment of RA since 2008, it was important to update recommendations now as the field strives to better control disease progression and improve quality of life,” said Jasvinder Singh, M.D., an associate professor in the UAB Division of Immunology and Rheumatology, principal investigator and project lead for 2012 guidelines. “The new guidelines for the first time offer guidance on how and when to switch between drug classes. They also stress the need for vaccination and screening to protect RA patients from infections such as shingles and tuberculosis and address the treatment of patients who also have cancer, hepatitis or heart failure.”
Though the recommendations vary with each patient, the new guidelines generally recommend physicians start treatment with a DMARD, proceed to therapy combining two or more DMARDs and then to a biologic when and if each option fails to control the disease. When switching from DMARDs to biologics, for example, physicians should use either an anti-TNF biologic or a non-TNF biologic if a patient “has moderate or high disease activity” after three months of methotrexate treatment or DMARD combination therapy.
Under the heading of high-risk patients, the guidelines recommend against the use of biologics in RA patients with untreated chronic hepatitis B because of the potential for strong side-effects. RA patients with cancer may be treated with a biologic if their treatment for a solid tumor happened five years earlier, and with heart failure if their case is not too severe.
Due to increasing awareness of the risk of preventable infections in RA patients, the recommendations place a priority on screening and vaccination. RA is an autoimmune disease in which the immune system attacks the body’s own tissues. Treatments suppress the immune system and make those treated vulnerable to infections.
For that reason, new guidelines recommend that all patients taking biologics for RA be screened for latent tuberculosis infection; 5 to 10 percent of these patients will go on to develop active TB later.
“A significant majority of RA patients ages 65 and older need vaccination against herpes zoster, also called shingles, and a new vaccine, Zostavax, has become available since 2008,” said Kenneth Saag, M.D., professor of medicine at UAB, project lead on the 2008 guidelines and senior author for 2012 update. “Not all patients are good candidates for the vaccine, however, and it currently can’t be used by patients taking biologics because it’s a live-virus vaccine. The field will need to continue studying the issue.”
Another subset of RA patients, women in their 20s, 30s and 40s, may be considering two HPV vaccines, also new since 2008, for protection against cervical cancer associated with that infection. They too will be asking their doctors how they can safely combine vaccinations with RA treatment.
The involved committees used a rigorous process to update the guidelines, which included a comprehensive, updated literature review and review by panels of international experts. UAB and UCLA undertook the administrative leadership functions for updating, developing and distributing evidence summaries, constituting panels, overseeing the consensus process and developing guidelines based on the evidence synthesis. Conclusions were then reviewed by more than 20 coauthors and 30 members of the ACR committees and the ACR Board of Directors.
Along with UAB and UCLA, contributing organizations included the University of Texas MD Anderson Cancer Center, University of Maryland, UCLA/RAND/West Los Angeles VA Medical Center, University of Nebraska, University of Pittsburgh, North Mississippi Medical Center, Hopital Cochin in Paris, Pacific Arthritis Center, Toronto General Research Institute, Healthy Motivation, Mayo Clinic, University of Minnesota and Park Nicollet Clinic, University of California at San Diego, Albany Medical College, Oregon Health and Science University and University of Michigan. The work was supported with a grant from the American College of Rheumatology.