Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects the joints, making them swollen, stiff and painful. RA will progressively destroy the joints without the use of pharmacological therapy to arrest and control the disease.
We don’t fully understand the cause of RA, but we do know that inflammation associated with RA occurs because the immune system is out of whack. Our immune systems protect us from infection, viruses, parasites and other threats by sending chemical messengers to fight them off. In people with RA, the immune system produces chemical messengers and inflammation when there’s no culprit to fight. Instead, the immune system fights the body’s own tissues. In the case of RA, this inflammation targets the joints.
The best way to find the right treatment for RA is to get an accurate diagnosis. That can take weeks, months, or even years. Typically, it takes us 3 to 6 months to convince ourselves that an early manifestation of RA is truly RA. Patients must understand that the diagnosis is a process over time–there’s no immediate gratification. But the disease can be difficult to diagnose, and we want to make sure we’re ruling out other possibilities before beginning treatment.
Once I’m certain of the diagnosis, then I’ll start the patient on a course of corticosteroids, like prednisone, for immediate benefit. The steroids decrease inflammation and slow down the immune system. Side effects of prednisone include weight gain, increased blood pressure, and increased blood sugar. At the same time, I’ll prescribe methotrexate, which can help with pain, swelling, and plays a role in slowing the progression of the disease. Side effects of methotrexate include GI upset, mild alopecia, and hair thinning. Methotrexate takes three months to work, so I’ll slowly get patients off the prednisone after a couple months and then increase the dose of methotrexate to tolerance. By six months, my goal is to have the patient’s RA controlled with methotrexate alone.
Methotrexate is the gold standard RA drug; about 30% of RA patients worldwide are well-controlled by methotrexate. But that means 70% of people will require an additional drug. If after six months we can’t get them off the prednisone–and we can’t control the RA with methotrexate alone–then I’ll add a biologic.
Biologics are drugs that are manufactured in a lab from biological material using humans or animals. Essentially, they’re antibodies that can block, at the molecular level, chemical messengers that cause inflammation. There are several biologics approved by the Food and Drug Administration (FDA) today:
TNF inhibitors that block a chemical messenger called Tumor Necrosis Factor (TNF) that contributes to inflammation, causing joint damage. Common TNF inhibitors include etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), golimumab (Simponi), and certolizumab (Cimzia).
B-cell inhibitors like rituximab (Rituxan) interfere with abnormal antibodies to reduce inflammation and control RA.
Interleukin-6 inhibitors like tocilizumab (Actemra) block a chemical messenger called interleukin-6 to stop production of inflammation.
Interleukin-1 inhibitors like anakinra (Kineret) reduce inflammation by blocking a chemical messenger called interleukin-1.
T-cell costimulatory blockers like abatacept (Orencia) interfere with signals that activate white blood cells called T cells in the immune system, preventing inflammatory immune system reactions.
Side effects of biologics vary, but include an increased risk of infection, which is why we will test patients for tuberculosis before starting therapy. Some biologics are given via injection, so patients may experience pain and rash at the injection site. The most common side effects with biologics given by infusion are flu-like symptoms.
Biologics are game changers. They’re the most dramatic advance in rheumatology in my lifetime, without question. They’ve been on the market for roughly 15 years now. I’ve been around to experience 15 years without biologics and about 15 years with biologics, and it’s very clear that they’ve changed many things about the management of RA. They reduce the amount of time people miss work, they reduce the number of joint replacements needed. Overall they’ve improved outcomes in many different ways.
There are limitations to biologics, however. They do have significant side effects, and they are fairly expensive. But there are many new biologics set to come to the market in the next few years, so they may become safer and more affordable in the future. In addition to biologics, I may also consider using a new drug called tofacitinib (Xeljanz), which is an oral drug called a JAK inhibitor. It works by blocking inflammation-causing pathways within the cell, whereas biologics block pathways outside the cell.
Aside from these medications, I also recommend non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil) or naproxen (Aleve) for mild pain. In some cases, I might inject a corticosteroid directly into the joint to provide instant relief. But these treatments will always be used in combination with methotrexate or biologics; those are the mainstays of therapy.
The most important part of treatment for RA is having a good relationship with your physician and trusting that he or she is making decisions to benefit you. As a rheumatologist, I’m constantly monitoring my patients’ conditions and deciding if adjustments need to be made. The field is rapidly moving and it’s incredibly exciting, so find a physician who is intuitive, paying attention to new therapies, and prescribing treatment that is best for your individual disease.
