While there have been many therapeutic advancements in drugs for rheumatoid arthritis (RA), it is still a condition without a cure. The primary aim of medications for RA thus becomes a slowing down of the progression of the disease or reaching remission by minimizing joint pain and improving quality of life.
A range of medications with different mechanisms of action compete in the RA marketplace, starting with the tried-and-true, anchor product methotrexate. Approved in 1988 to treat RA, it is a disease-modifying antirheumatic drug (DMARD), which suppresses the immune system and can be even more efficacious when combined with other RA medications.
A trio of biologics hit the market around the turn of the century—Humira (adalimumab), Remicade (infliximab) and Enbrel (etanercept), all TNF (tumor necrosis factor) inhibitors in 1998, 1999 and 2002, respectively. TNFs suppress the physiologic response to tumor necrosis factor, which is part of an inflammatory response.
JAK inhibitors—the first one approved for RA patients was Xeljanz (tofacitinib) from Pfizer in 2012—have picked up the slack for some patients who have an inadequate response to DMARDs.
A relatively new entry into the RA market is Kevzara (sarilumab), a human Interleukin-6R inhibitor (IL-6R) that suppresses the action of the IL-6R in RA. IL-6R can trigger chronic inflammation, causing tender and swollen joints, reduce physical function and destroy bone and cartilage associated with RA. Manufactured by Sanofi and Regeneron, it has been approved in this country, Canada, and the European Union.
Actemra (tocilizumab) is the only other IL-6R currently on the market. Johnson & Johnson’s sirukumab failed to make the cut, when the manufacturer decided not to respond to FDA requests for further clinical data.
These drugs are often used when DMARDs and TNFs have proved ineffective or intolerable.
Lynn Ludmer, MD, rheumatologist at Mercy Medical Center in Baltimore, considers RA complex to treat because of the difficulty in identifying who will become disabled and in determining which patients will respond to a specific medication, and the limited effectiveness of certain medications.
“RA is a spectrum of disease for which patients respond to one drug or another,” says Nathan Wei, MD, a rheumatologist in Frederick, Maryland. “It is difficult to predict what the target is in any given patient. We are not aware ahead of time what to do next. How it manifests itself, however, is fairly typical—affecting a body’s small joints.”
Like Wei, Alejandro Badia, MD, a hand and upper extremity surgeon and the CEO of Badia Hand to Shoulder Center in Doral, Florida, sees RA as more than just a form of arthritis. “It should be considered a systemic disease process that is autoimmune, in which the body attacks itself and in this case, affects the joints.
“The challenge with [traditional RA treatments] is that they come with complications as their role is to essentially suppress the immune system,” he says. “Newer treatments are directed at improving these drugs and also minimizing their side effects.”
Wei says that “treating to target” is one of the most effective ways to address RA. The strategy includes:
- Setting a specific testing goal that signals either remission or low disease state.
- Testing monthly to monitor progress.
- Switching medication regimen promptly if progress isn’t made.
- Monitoring progress regularly.
Wei recommends starting patients off with methotrexate and depending on the response, switching to biologics.
Carole Huntsman, head of multiple sclerosis, oncology and immunology, North America Sanofi Genzyme, agrees with Wei. She believes there is evidence that patients can respond better when switching to a biologic with an alternative mechanism of action rather than continuing to cycle between TNF inhibitors.
On the other hand, Ludmer is not convinced that biologics work better than their predecessors and JAK inhibitors. She says she needs more studies proving their effectiveness.