Rheumatoid Arthritis Treatment Guidelines

By Linda Rath

The American College of Rheumatology (ACR) has published its new 2020 guideline for rheumatoid arthritis treatments. The ACR updates its guideline for the treatment of rheumatoid arthritis (RA) every few years. The last changes appeared in 2015. Since then, new drugs have hit the market, older drugs have been reassessed, and there’s more evidence for the role of nondrug treatments for RA.

Of 44 recommendations, only seven were considered strong, meaning there’s clear evidence that the benefits of the treatment outweigh the risks and most patients endorse them. The remaining recommendations are called conditional because they lack good evidence one way or the other. The new guidelines don’t address vaccinations — particularly relevant right now — or nondrug therapies like diet and exercise. Those are expected in a later update.

Here are some of the main takeaways:

Methotrexate is a conventional disease-modifying anti-inflammatory drug (DMARD). It works to lower inflammation and slow an overactive immune system, which occurs in rheumatoid arthritis. The new guidelines strongly recommend methotrexate alone (monotherapy) as the first treatment for people with moderate to high disease activity who haven’t taken DMARDs before. Methotrexate monotherapy is strongly recommended over other conventional DMARDs, a biologic DMARD like adalimumab (Humira) and small-molecule drugs such as Janus kinase inhibitors (JAKs), including baricitinib (Olumiant), tofacitinib (Xeljanz) and upadacitinib (Rinvoq). Methotrexate monotherapy is also strongly preferred over combination treatments. The conventional DMARD hydroxychloroquine is conditionally recommended for people with mild symptoms.

Methotrexate pills are conditionally recommended over injections. To ease GI side effects, the ACR recommends lowering or splitting the dose or increasing the amount of folic acid patients take. For patients who don’t improve with methotrexate pills, switching to methotrexate injections instead of another conventional DMARD is conditionally recommended. “There’s a strong push for methotrexate monotherapy before switching to other drugs,” says Liana Fraenkel, MD, director of patient centered population health research at Berkshire Medical Center and principal investigator for the guideline.

Biologics are DMARDs made from living cells. They’re stronger, far more expensive, and harder to administer than conventional DMARDs like methotrexate. In the past, they were used in combination with methotrexate when methotrexate alone didn’t work well enough. In the new guidelines, methotrexate monotherapy is strongly preferred over methotrexate plus a biologic other than a tumor necrosis factor (TNF) blocker. It’s conditionally recommended over methotrexate combined with a TNF blocker. Methotrexate plus a biologic is preferred over triple therapy (combined methotrexate, hydroxychloroquine and sulfasalazine), mainly because it’s faster-acting.

In an effort to greatly limit the use of corticosteroids, even as a bridge treatment, the guidelines strongly recommend against long-term steroids and conditionally recommend against short-term steroid use. For patients who need steroids to reach a treatment goal, such as low disease activity, adding or switching DMARDs instead of continuing with steroids is conditionally recommended. “Even lower doses of prednisone can be harmful,” Dr. Fraenkel says.

Although there’s not much evidence to support it, a treat-to-target approach is strongly recommended for patients who haven’t taken biologics or small molecule drugs. In treat-to-target, doctors and patients decide on a goal and adjust treatment until the goal is reached. Though everyone hopes for remission, many patients may not be able to achieve it. A more realistic aim is low disease activity, which keeps symptoms under control and helps maintain a good quality of life. Still, the guideline states the goal should be tailored to each patient and remission can be the target when possible.

According to the guidelines, doctors and patients can consider tapering medications if patients have maintained their target for at least six months. Dose reduction is conditionally recommended over gradual discontinuation and gradual discontinuation is conditionally recommended over stopping therapy abruptly. This is one area where patients and doctors on the expert panel disagreed. Doctors want patients to stay on medications; patients want to get off them.

These drugs are similar in safety and effectiveness to already-approved biologics but have different names and should potentially cost less. Biosimilars are created by slightly changing the manufacturing process used for the original or reference drug. The 2020 guideline acknowledges the safety and efficacy of biosimilars and encourage their use — a shift from the ACR stance in 2015. One hurdle to broader use of biosimilars is that insurers have been reluctant to pay for them. In 2019, insurers approved a biosimilar before a biologic just 14% of the time. Plus, copays for biosimilars are often about the same as for the reference drug. Whether biosimilars will really make biologics more affordable remains to be seen.

The most important factor in all treatment considerations is shared decision-making, where patients are informed of all their options, including nondrug ones, and have a full voice in their own care. “Patients were involved in every step of the process [of creating the update], and the recommendations truly reflect their perspectives,” Dr. Fraenkel says.

Read more about the ACR guideline.