Researchers comparing drugs to treat rheumatoid arthritis found that combining one synthetic drug with one of six biologic medications often works best to reduce joint swelling or tenderness in patients with rheumatoid arthritis, the Agency for Healthcare Research and Quality (AHRQ) reported.
In a comparative effectiveness review of 103 published studies, AHRQ-funded researchers from the RTI International-University of North Carolina Evidence-based Practice Center in Chapel Hill analyzed the benefits and harms of synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs and corticosteroids in treating adults with rheumatoid arthritis, an autoimmune disease that affects about 2.1 million American adults. About 9 million physician office visits and 250,000 hospitalizations each year in the U.S. are attributed to rheumatoid arthritis, AHRQ reported.
Half of the studies reviewed were funded by pharmaceutical firms, the agency said. About 20 percent of the studies were supported by the government or independent sources, and 11 percent were supported by a combination of pharmaceutical and government funding. Researchers could not determine the funding source for the remaining 19 percent of the studies used in the review.
In the AHRQ report, researchers concluded that combining methotrexate, a synthetic DMARD, with one of the biologic DMARDs - Orencia (abatacept), Humira (adalimumab), Kineret (anakinra), Enbrel (etanercept), Remicade (infliximab) or Rituxan (rituximab) - works better than using methotrexate or a biologic DMARD alone.
The investigators also found that methotrexate works as effectively as the biologic DMARDs Humira and Enbrel for patients who have early rheumatoid arthritis. However, researchers said, Humira and Enbrel showed better short-term results as measured by X-rays of joints.
AHRQ said that not enough evidence exists to determine whether combining two biologic DMARDs is more effective than using one of those products. However, the agency warned, combining two biologic DMARDs can increase the risk of serious infection.
About 17 of every 1,000 people taking a biologic DMARD for three to 12 months develop a serious infection, AHRQ reported. Among biologic DMARDs, rates of painful injection site reactions are more common for Kineret than for Enbrel or Humira, researchers noted. Combining prednisone with the synthetic DMARD hydroxychloroquine, methotrexate or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function, investigators said.
Researchers found no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine. In addition, investigators said, combining the synthetic DMARDs methotrexate and sulfasalazine is no more effective than using just one of the medications for patients with early rheumatoid arthritis.
AHRQ said that more long-term research was needed on rheumatoid arthritis medications, including how the outcomes of the drugs vary among patients with different health conditions and demographic characteristics.
The agency called for more comparative studies on various combinations of drugs.
In addition, the agency said, more research is needed about whether taking the medications earlier, particularly biologic DMARDs, results in better long-term outcomes.
FDA Studies New Advisory Committee Rules
The FDA has issued two draft guidance documents on advisory committee procedures that affect the way potential conflicts of interests are disclosed and the manner in which panelists vote.
The agency routinely grants waivers to panelists with potential conflicts of interests and informs the public of those waivers at least 15 days before a committee meets. However, under current rules, the complete details of those conflicts typically are not disclosed to the public.
The agency has been criticized in recent years by lawmakers and consumer advocacy groups for allowing panelists with conflicts to participate on advisory committees.
An April 2006 study published in the Journal of the American Medical Association reported that in 73 percent of advisory committee meetings studied, 28 percent of panelists overall disclosed a conflict but only 1 percent were recused from participating at a meeting.
Under a proposed guidance document issued by the FDA, regulators want panelists to complete a form acknowledging the type, nature and magnitude of any disqualifying financial interests for which a waiver is sought and giving the agency permission to publicly disclose that information.
If the FDA grants a waiver, the disclosure form would be posted on the agency's website at least 15 days before a committee meets. That proposed procedure, the FDA said, would make the advisory committee process "more transparent and consistent."
The second draft guidance document recommends that voting at advisory committee meetings be done simultaneously rather than sequentially. A simultaneous vote, the agency contended, would help avoid any potential order bias associated with sequential voting and "thereby enhance the integrity and meaning of the voting results."
Members of advisory committees typically communicate advice or recommendations to the agency at meetings by sharing their individual thoughts during a discussion of a particular matter and also by voting on a question or series of questions posed by the FDA to the panel.
The FDA is not required to take its committees' advice, but generally does. Since both of the new procedures were issued in the form of a draft guidance document, which are meant as merely suggestions and recommendations about the FDA's current thinking on a topic and not legally enforceable, it is unclear how the agency intends to enforce the proposed procedure changes. Both documents are open for public comment until mid-January.
Panel Probing GSK Intimidation Allegation
Sens. Max Baucus (D-Mont.) and Charles Grassley (R-Iowa) have asked former GlaxoSmithKline research executive Tadataka Yamada to provide information to the Senate Finance Committee about reported attempts to bully an independent scientist who voiced concerns about the safety of GSK's diabetes medication Avandia (rosiglitazone).
As part of its ongoing investigation of Avandia, the finance committee is examining the evidence surrounding allegations that London-based GSK in 1999 sought to intimidate John Buse, a professor of medicine at the University of North Carolina, in an attempt to discourage the scientist from publicly voicing concerns about the increased risk for adverse cardiovascular events in patients using Avandia.
In a Nov. 16 letter, Baucus, chairman of the committee, and Grassley, the ranking member, asserted that Yamada, now head of global health at the Bill and Melinda Gates Foundation, "played a significant role in developing and implementing GSK's strategy for dealing with Dr. Buse's public airing of his concerns about cardiovascular risks associated with Avandia."
The lawmakers gave Yamada until Nov. 30 to respond to their request to have committee personnel interview him about any involvement he may have had in the reported intimidation of Buse.
The FDA on Nov. 14 announced that new warnings had been added to the existing black box on Avandia's labeling warning that patients with Type II diabetes taking the drug, especially those who have underlying heart disease, are at an increased risk for a heart attack.
Lawmakers Seek Ban On Hybrids
Sens. Sam Brownback (R-Kan.) and Mary Landrieu (D-La.) have introduced the Human-Animal Hybrid Prohibition Act, a bill that, if enacted, would make creating part animal, part human beings illegal. Currently there is no regulation preventing the creation of human-animal hybrids. The bill seeks to prohibit combining human and animal eggs and sperm to create a hybrid embryo, inserting animal DNA into a human embryo and creating an animal with human reproductive organs or a human brain. Brownback previously had introduced similar legislation in 2005.