“My mantra here is to make the punishment fit the crime,” she said. “If somebody comes in with a couple of [affected] PIPs [proximal interphalangeal joints] and everything else is well controlled, I’m not going to add a $40,000 drug to control a couple of PIPs. I’m going to add something like hydroxychloroquine.”
Which second DMARD should you add when methotrexate proves inadequate? Answers could come from biomarkers, but no useful biomarkers for this question yet exist, Dr. Bathon said.
“We need a series of biomarkers, whether they’re genetic or proteomic, to help guide us on therapy,” she said. Otherwise, this decision will rely on comparative effectiveness study results (there are relatively few), assessing patient subsets that might respond better to particular agents, disease severity, patient preferences, cost [of therapy] and insurance considerations.
One area of comparative-effectiveness research brings an important lesson: Methotrexate plus a tumor necrosis factor (TNF) inhibitor may be no better than the triple therapy of methotrexate, sulfasalazine and hydroxychloroquine. This result was found in both the blinded TEAR and the blinded RACAT trials; although the unblinded Swefot study found superiority for the anti-TNF combo in the first 12 months, the advantage was no longer seen at 24 months.2,3
“When you’re thinking about what drugs to use, triple therapy is pretty successful,” said Dr. Bathon. “It’s not used much in the U.S., but it is used heavily in Europe and Canada.”
Looking Ahead
Biosimilars are on the horizon, and they may cost less—although this has been at least somewhat counterbalanced by discounts on the bio-originator drugs they’re based on, Dr. Bathon said.
The prospect of forced switches from an original drug to a biosimilar looms, but the FDA hasn’t approved this interchangeability concept yet. Trials assessing multiple switches in individuals are now required, and there is “not a lot of enthusiasm” for doing those trials, she said.
In a separate discussion with clinicians, Dr. Bathon stepped into the difficult terrain of RA and interstitial lung disease (ILD), with which many in the room said they’d struggled.
“What’s effective for ILD isn’t necessarily effective for the joints, and vice versa,” she said. “So what I try to do in that case is get the joints under control with one agent and then use something else for the lungs. But what do you use for the lungs?”
Mycophenolate mofetil (MMF) and rituximab have only been examined in open-label studies and the efficacy data are inconsistent, she said. But randomized clinical trials are now in progress in RA-ILD to evaluate the kinase inhibitor nintedanib and the anti-fibrotic agent pirfenidone.