“Evidence is insufficient to draw firm conclusions.”
“We did not find any head-to-head randomized controlled trials.”
Those are phrases that commonly appear in a 151-page report, based on a literature review and released by the Agency for Healthcare Research and Quality, titled “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults.”
“The gaps in information for specific [rheumatoid arthritis] therapies are substantial,” wrote the researchers of the RTI International-University of North Carolina Evidence-Based Practice Center, under contract to AHRQ, a part of the U.S. Department of Health and Human Services.
Despite the paucity of data, the researchers draw some conclusions from the best available medical literature about the benefits and harms of three classes of medications for rheumatoid arthritis (RA) and psoriatic arthritis: synthetic formulations of disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.
For example, they found that combining the synthetic DMARD methotrexate with one of the biologic DMARDs (abatacept, adalimumab, anakinra, etanercept, infliximab, or rituximab) works better to lessen joint damage than does using methotrexate or one of the biologic DMARDs alone.
In addition, they found that methotrexate works as effectively as adalimumab and etanercept for patients with early RA. “Radiographic outcomes, however, were statistically significantly better in patients treated with biologic DMARDs than [in] patients treated with methotrexate,” the researchers wrote.
“How such intermediate outcomes translate to the long-term clinical progression of the disease remains unclear.”
Dr. Steven B. Abramson, director of the division of rheumatology at New York University Medical Center, called the report “very comprehensive and useful” and “reflective of what I think is our common practice. It tries not to tilt toward one therapy or another. It's a good summation of several years of literature.”
Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, Mo., called the report a “good start” and acknowledged the challenge researchers faced in assembling a document “when there is such precious little data comparing therapies directly.
“That's always a limitation of any of these studies, yet clinicians are forced to make these comparisons all the time,” according to Dr. Leonardi.
The team of researchers, led by Dr. Katrina E. Donahue of the department of family medicine at the University of North Carolina at Chapel Hill, reviewed 156 articles in the medical literature based on 103 studies of synthetic DMARDs, biologic DMARDs, and corticosteroids. Of these, 50% were supported by pharmaceutical companies, 20% were supported by government or independent funds, 11% had a combination of pharmaceutical and government funding, and the source of funding could not be determined in the remaining 19% of studies.
Most of the studies were found to be of fair quality, which was defined as susceptible to some bias but probably not sufficient to invalidate their results. Only one-quarter of the studies were rated good quality, which was defined as having the least bias and results that are considered to be valid.
Based on their literature review, the researchers found that combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function. They also determined that there are no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine.
Other findings in the report include the following:
▸ There is not enough evidence to conclude that combining two biologic DMARDs is better than using one biologic DMARD.
▸ An estimated 17 out of every 1,000 people who take a biologic DMARD for 3-12 months develop serious infection. Combining biologic DMARDs increases this risk.
▸ Painful injection-site reactions occur more often among patients who take anakinra (67%), compared with those who take etanercept (22%) or adalimumab (18%).
Dr. Leonardi, who has helped run clinical trials of biologic DMARDs for psoriasis patients, said that while the current data on comparative treatments for RA and psoriatic RA might be limited, dermatologists “have a long way to go” in comparing biologic DMARDs for psoriasis. “We're left to try our own meta-analysis based on safety and efficacy and looking at the types of patients that come into the trials, [asking] how well did things perform? What were the comparable end points at 12, or 14, or 16 weeks? We try to make our own assessments as best as we can without those head-to-head trials. We just don't have that degree of sophistication yet.”
In the report's conclusion, the researchers emphasized the need for long-term studies of arthritis medications, including head-to-head trials “assessing combination therapies involving synthetic DMARDs in comparison with those involving biologic DMARDs,” they wrote. “Adequately powered, long-term [randomized clinical trials] must also examine different treatment strategies with and without corticosteroids, synthetic DMARDs, and biologic DMARDs to determine the best therapy to prevent or minimize debilitating joint damage in patients with RA. Additionally, no head-to-head [randomized clinical trials] have compared one biologic DMARD with another; this is a significant hole in the literature that future research should fill. However, this is less likely to occur because of the expense of biologic DMARDs.”