Treating rheumatoid arthritis, a chronic autoimmune disease that causes joint stiffness, swelling, and pain, has never been a one-size-fits-all prescription. Every patient responds to treatments differently, and fortunately, there are now more drug options available than ever.

Historically, drugs called “synthetic conventional disease-modifying anti-rheumatic drugs,” nicknamed csDMARDs, were the first line of defense for treating RA. In many patients, these agents could reduce or reverse symptoms of the disease, and slow the progression of joint damage. But csDMARDS like methotrexate (which is the most common) don’t work well for all patients. Beginning in 1989, physicians began to pair csDMARDs with new biologic drugs that boosted the treatment’s effectiveness in many patients. As newer biologics have come onto the market, rheumatologists are finding that for patients who cannot or should not take csDMARDs, prescribing biologics alone as “monotherapy” is a valid treatment option.

Right now, the guidelines of both the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) suggest using biologics only in combination with the csDMARDs. One reason is that the first biologics developed, called “anti tumor necrosis factor inhibitors,” didn’t work as well without the csDMARDs. The two types of drugs act synergistically to improve the effectiveness and response rate. Recently, newer biologic drugs have been developed that show comparable efficacy in combination with DMARDs or when used alone.

While the combination of drugs is still the gold standard of treatment, biologic monotherapy is an important option for patients who are intolerant to csDMARDs, or who develop side effects that preclude their use. Patients who have some sort of liver disease, such as hepatitis, or who drink more than the occasional cocktail or glass of wine, aren’t good candidates for csDMARDs, for example, since methotrexate tends to worsen any existing problems with liver function For these patients, treatment with biologic agents alone can help fight the disease while sparing them undesirable side effects.

While most physicians still prescribe a combination of drugs, many patients prefer monotherapy. Between 80 and 90 percent of all patients who are prescribed a biologic treatment are also prescribed a csDMARD, according to physician surveys. Yet data from healthcare claims shows that when the two therapies are prescribed together, more than half of the patients do not pick up their methotrexate prescriptions. One reason for the lack of compliance may be ease of delivery: patients take the biologic drugs in their doctor’s office, every week or month, either as a subcutaneous shot or an IV infusion, while they have to remember to take oral methotrexate pills much more frequently at home. Some patients actively discontinue the use of the DMARDs because they don’t believe they’re necessary; if their disease is being effectively controlled with the biologics, they feel no need to take another drug.

Today, about 30 percent of patients taking biologics are taking them as a monotherapy. This number suggests a sea change in treatment options for the disease. In its 2013 guidelines, the EULAR Task Force recognized that there is some supportive data for using certain biologics as a monotherapy, although it maintained that they should continue to be used with csDMARDs. But when csMARDS are not an option, monotherapy is a clinically valid and proven alternative. Currently, over a hundred clinical studies are focusing on exploring the use of monotherapy treatment for rheumatic diseases to help understand when it is most appropriate for which patients.