Choosing the Right Medication

Combined with a treat-to-target approach that we discussed in our last episode, advances in treatment over the last several years have greatly improved outcomes for those of us who have RA. There's no known cure for RA yet. Instead, treatment now focuses on stopping the progression of disease, what are the goals of therapy, and where do the various therapies fit in achieving them.

The goals of RA therapy have changed dramatically over the last decade to aim for achieving early and persistent remission, or low disease activity, which can mean improvement in patient symptoms, functionality, quality of life, and even survival. Drug treatments for RA fall into two main types, those that provide symptomatic relief and those so-called Disease-Modifying Anti-inflammatory Drugs, or DMARDs.

Nonsteroidal Anti-inflammatory Drugs, or NSAIDs, such as ibuprofen, are commonly used to reduce pain and inflammation, but they don't slow the progress of RA. In contrast, DMARDs are designed to affect the underlying joint damage and the course of RA. What we've seen over the last several years is a shift in strategy towards earlier, more aggressive use of DMARDs and new classes of disease-modifying biologic medications that target the specific pathways responsible for RA.

Most people with moderate or severe RA, myself included, are prescribed methotrexate early in the course of their disease. This DMARD has been a mainstay of therapy for over three decades. Where does it stand now?

The updated 2021 American College of Rheumatology Guidelines still recommend methotrexate as the initial therapy for those patients with moderate to severe RA who have not had a DMARD before. Methotrexate works to suppress the immune system as a whole and reduce the inflammation and joint destruction that occurs in RA. Physicians often prescribe corticosteroids for fast and temporary relief of pain and inflammation at the start of DMARD therapy or during a painful flare-up. Updated guidelines, however, recommend avoiding these drugs wherever possible because of potential side effects.

Advances in our understanding of RA have led to a newer class of DMARDs called biologics. These drugs work by targeting specific steps in the RA inflammatory process. What are these agents exactly, and where do they fit?

ALLAN GIBOFSKY: When conventional DMARDs are insufficient to control disease activity, the next step is a biologic. These therapies are genetically engineered agents that target specific parts of the immune system to block RA inflammation, potentially working relatively quickly to ease joint pain and swelling and also prevent further joint damage. Whereas conventional DMARDs like methotrexate offer a more broad approach, biologics zero in on specific pathways that drive inflammation. These include drugs that inhibit tumor necrosis factor, which plays a role in triggering inflammation, or other interleukin proteins that likewise have a role in inflammation.

Some of these agents may also block T-cell or B-cell activity, both of which are involved in the body's immune system and inflammation. Inflammatory diseases like RA are often driven by several factors, so there is no one-size-fits-all therapy. A treat-to-target approach can help in selecting the appropriate biologic if the first one a patient tries doesn't work or at some point stops working.

The newest class of RA drugs to gain FDA approval are called Janus Kinase, or JAK, inhibitors. These medications, which are taken orally, work inside cells to stop the inflammatory process.

ALLAN GIBOFSKY: The autoimmune and inflammatory processes that underlie RA involve a complex biochemical signaling system. While biologics interfere with signaling that stimulates inflammation from outside the cell, JAK inhibitors work by interfering with specific pathways inside the cell. These small molecule drugs help block the immune system from creating specific JAK enzymes that drive the pro-inflammatory cellular responses seen in RA. This latest class of JAK inhibitors are DMARDs. They're designed to help slow the progression of RA and prevent further joint damage.

Medicines often work better when combined with lifestyle changes. Please join me next time when we explore things that you can do to improve RA and your ability to cope with it.