Methotrexate is the gold standard drug used to treat rheumatoid arthritis (RA). About 30% of RA patients worldwide are well controlled by methotrexate alone. It’s part of a class of medications called disease-modifying antirheumatic drugs (DMARDs). While we don’t completely understand how it works in RA, methotrexate reduces inflammation and slows the progression of the disease by suppressing immune system activity. It typically takes 3 to 4 months to feel the full effects of methotrexate, but if after six months, a patient’s RA symptoms haven’t been alleviated, I’ll decide to try something else. Around 70% of patients require an additional therapy in combination with methotrexate, or instead of methotrexate. If you’re one of these patients, the physical signs are typically clear. If after six months of treatment, I can see no significant improvement–your joints continue to be swollen and red, they’re starting to become deformed, you’ve lost a lot of function, many joints are affected–I’ll be able to recognize that your disease is very aggressive. In addition to noting your physical symptoms, I’ll use different clinical parameters to decide how to move forward with treatment. I’ll take a medical history; perform a physical exam; ask questions about your level of function; and order X-rays, ultrasounds and blood tests. We use these tools to follow scientific reasoning, but often it’s very apparent when the patient is not doing well. However, sometimes it’s not clear from symptoms and sometimes there could be another diagnosis contributing to the problem; perhaps the patient is depressed or going through a highly stressful time. That’s why it’s important that as a physician, I don’t immediately assume patients are symptomatic because of their disease alone. There might be something else at play to consider, and treating their RA may not get to the underlying issue. That’s where a physician’s clinical experience becomes crucial. If, however, I determine that the patient’s symptoms are a result of an aggressive form of RA, I act quickly. Most of the damage in the disease occurs early, and I want to take immediate action. In most cases, I’ll choose to add a medication called a biological response modifier, also known as a biologic. Biologics are the most dramatic advance in rheumatology in my lifetime, without question. Biologics are derived from human or animal material, and they target and block processes that create inflammation at the molecular level. They are game changers. Biologics reduce the amount of time people miss work, they reduce the number of joint replacements, and they’ve improved RA outcomes in many other ways. There are currently nine biologics approved by the Food and Drug Administration (FDA) to treat RA: Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Golimumab (Simponi) Certolizumab (Cimzia) Rituximab (Rituxan) Tocilizumab (Actemra) Anakinra (Kineret) Abatacept (Orencia) 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 do have limitations: They come with side effects and they cost a lot of money. But they’re a result of an exploding field of research in which scientists are looking to see how they can manufacture drugs that interfere with the molecular biology of RA patients at a very specific level. Many new biologics are going to come to the market over the next several years. They’ve changed how RA and other diseases are treated, and study after study shows they’ve greatly improved the lives of people with RA.