Biologic DMARDs

The introduction of disease-modifying anti-rheumatic drugs (DMARDs) has revolutionized treatment of RA, and one that has significantly broadened and improved the drug treatment options for patients. DMARDs can change or modify the disease course in RA and slow or prevent damage to joints and related structures. There are different types of DMARDs: conventional, biologic, and target-specific. Biologic DMARDs are bioengineered proteins that mimic functions found in specific human genes or cells. They work by interfering with specific substances in the immune system to reduce or better regulate the inflammatory responses that cause RA.1,2

Biologics used in RA are proteins that come from human genes. In contrast to conventional DMARD treatments, which act on the immune system as a whole, biologics are engineered to target specific molecules on immune system cells, such as receptors on T- or B-cells, to block the actions of these cells and, thereby, dampen the out-of-control inflammatory process that characterizes an autoimmune disease like RA.2

There are several types of biologics currently available to treat RA. They are classified according to which molecules they target and include2-3:

  • Tumor Necrosis factor (TNF)-inhibitors (also called anti-TNF agents)
  • B-cell inhibitors
  • T-cell inhibitors
  • Interleukin-6 (IL-6) inhibitors
  • Interleukin-1 (IL-1) inhibitors

TNF-inhibitors are the largest groups of biologics now available to treat RA and include:

Other biologic DMARDs work in different ways, including:

How are biologics used in RA?

Evidence from clinical trials supports the use of biologics in four scenarios2:

  • For prevention of RA
  • As first-line treatment in early active RA
  • After failure of methotrexate or other conventional DMARDs
  • After failure of one type of biologic (typically TNF-inhibitors are used first)

When should I start on a biologic treatment?

The decision of when to use a biologic to treat RA is a complex one that depends on several factors, including how active your disease is, whether you have already tried other conventional treatments that are considered the first option in RA treatment, and cost considerations. You and your doctor will work together to determine when and if a biologic treatment is appropriate for you. While biologic DMARDs are typically used after patients have not gotten a good response from conventional DMARDs, in some patients with aggressive disease, biologics may be used as a first-line treatment.1,2

How do different biologics compare?

There have been no head-to-head trials of biologic treatment in RA, and it is difficult to compare results from different trials due to differences in patient groups involved (patients vary from trial to trial in severity and duration of disease). However, there have been some systematic comparisons of results from existing randomized, controlled clinical trials of different biologics. One review considered five different biologics, infliximab, rituximab, etanercept, adalimumab, and abatacept.5 All of these agents were significantly more effective than placebo in achieving disease control, defined as the rate of ACR50 response (the percentage of patients who improved by 50% in ACR disease activity criteria). There were no significant differences between individual biologics in terms of rates of ACR50 response. However, when individual agents were compared, some were more likely than others to result in this level of disease control.2

How long does a biologic take to achieve full effect?

Biologics take somewhat less time to achieve full effect than traditional DMARDs, with time to effect ranging from 4 to 8 weeks or occasionally earlier, depending on the specific drug. Most biologics must be taken by injection or intravenous (IV) infusion. Some are available for injection through the skin and may be taken at home. Others must be infused at your doctor’s office, with an infusion taking anywhere from 1 to 6 hours.1

How effective are biologic treatments?

Although individual biologics act differently and one may be more useful in an individual patient than another, we can make some generalizations about their effectiveness in RA. Based on results from existing randomized, controlled trials, biologic treatment were significantly more likely to result in control of disease activity, defined as either ACR20, 50, or 70 response, than placebo. They were also significantly more likely to result in responses and remission, defined as improved disease activity score (DAS).2

Another key outcome from clinical trials of biologics is radiographic progression. Clinical trials have shown strong evidence that biologics reduce the progression of joint erosion. One systematic review compared the effect on radiographic progression of biologics combined with methotrexate alone and found that biologics resulted in a significant decrease in the rate of progression and joint damage above and beyond methotrexate.6

Does the combination of a biologic with methotrexate increase efficacy?

A key systematic review of results from existing randomized, controlled trials in which a biologic was combined with methotrexate found that there was no evidence that the combination resulted in a greater likelihood of achieving an ACR50 response. The analysis considered 20 trials in which a biologic and methotrexate were given and 7 trials in which a single biologic treatment was used. Patients in the studies who received the combination were 3 times more likely than placebo to achieve an ACR50 response, while those who received a single biologic treatment were 4 times more likely than placebo to achieve an ACR50 response.5

What are the side effects and safety issues with biologic treatments?

While individual biologics have distinct safety profiles and the risk for specific side effects varies by agent, there are some common safety concerns with these drugs. Remember, biologics by design are intended to dampen the immune response. Therefore, these drugs may increase the risk of infections and cancers, the very health problems that the immune system defends against. This increased risk may be small for most patients, with the benefits of biologic treatments far outweighing the risks.2

The most common safety concerns with biologics include increased risk of infection, infusion or injection reactions (for those drugs that are taken by IV or injection), increased risk for certain types of cancer, the development of antibodies that neutralize the effect of the drug, and other autoimmune disorders (eg. lupus-like syndromes). It is useful to check the safety profile of individual biologic treatments to determine the risk for these safety problems.2

Written by: Jonathan Simmons and Emily Downward| Last reviewed: June 2018.
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