LAS VEGAS – The future looks bright for lupus treatment given the extensive list of drugs and targets currently undergoing evaluation, but for now treatment remains largely an art, according to Dr. Richard Furie.
"We try to integrate science, but it really is an art – these patients are very difficult," he said at the meeting.
That’s because of the heterogeneity of the disease, and the need to balance the benefits of treatment against the potential harms, which are extensive with currently available drugs, he explained.
Success is best achieved by "getting back to basics," he added.
First, as simple as it sounds, "do good" by controlling disease activity, preventing damage from disease, and preventing flares – as even one flare can cause damage – and "do no harm," which requires preventing damage from treatment and avoiding the treatment of damage with agents intended for active disease, he said.
"This is difficult, but the last thing we want to do is bombard a patient with potentially toxic medication when they are not going to reverse damage. ... We have a lot of potentially harmful medications. ... The name of the game is to minimize damage over time," said Dr. Furie, chief of the division of rheumatology at North Shore–LIJ Health System and professor of medicine at Hofstra North Shore–LIJ School of Medicine in Hempstead, N.Y.
Dr. Furie outlined his principles for treatment design:
• Identify disease manifestations.
• Distinguish activity from chronicity. For example, it is important to determine if a rash represents active disease or a scar, and whether proteinuria represents active nephritis or previous damage.
• Prioritize active disease manifestations.
• View disease activity as a continuum.
• Treat with the least toxic medicine and the lowest dose needed to address the most concerning disease manifestation. This will hopefully bring other manifestations under control as well, but treating too aggressively can lead to unnecessary damage, he said.
As for currently available treatments, "we’ve come a long way and patients are doing better," he said.
But the number of medications remains limited, and a great deal more work must be done, particularly with respect to lupus nephritis.
"At best, we do a good job with treatment in about 30%-40% of [patients with lupus nephritis], so in more than half we’re not doing well," he said.
More efficacious therapies are also needed for severe extrarenal lupus, flare prevention, and remission induction, he said, noting that treatments that are safer than steroids and cyclophosphamide also are needed.
Among currently used treatments, rituximab, while promising in open-label studies and off-label experience, has had disappointing results in randomized, controlled clinical trials. It nonetheless remains "in the toolbox," Dr. Furie said, noting that interest remains high in studying the agent for nephritis.
Mycophenolate mofetil also has been disappointing, in that it failed to show superiority to cyclophosphamide in the Aspreva Lupus Management Study (ALMS). However, Dr. Furie classified this drug as a "successful failure," because ALMS demonstrated what many had already believed – that mycophenolate mofetil is a good drug for lupus nephritis (J. Am. Soc. Nephrol. 2009;20:1103-12) .
Another agent, belimumab, on the other hand, represents a success story – and a history-making success story at that, he said.
Belimumab was the first drug approved for SLE via a randomized controlled trial, he explained, noting that it has favorable effects on steroid tapering to under 7.5 mg/day, 36-Item Short Form Health Survey (SF-36) fatigue scores, flare rates, and DNA antibody and complement levels – all with a favorable safety profile.
Unfortunately, the failures outweigh the successes with respect to the "humbling process" of drug development, but many drugs and targets are currently being investigated, he said.
In fact, there are more studies than there are patients, he said, adding, "but it still strikes me how many companies want to go forward in lupus, and I think it’s great for the field."
"There are a lot of interesting drugs on the horizon. ... We will someday have biomarkers, personalized therapy, and better outcomes," he said at the meeting, held by Global Academy for Medical Education. GAME and this news organization are owned by Frontline Medical Communications.
Dr. Furie reported receiving research support and/or serving as a consultant or investigator for several companies, including AstraZeneca, Biogen Idec, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, and Novartis. He also has received research support from the National Institute of Allergy and Infectious Diseases.