Is Tapering Biologic Drugs Beneficial in Patients with Rheumatoid Arthritis?

Patients with early stage rheumatoid arthritis may benefit from tapering DMARD therapy.

Whether biologic disease-modifying antirheumatic drugs (DMARDs) should be tapered in patients with rheumatoid arthritis who have achieved low levels of disease activity was the focus of a debate at the American College of Rheumatology and Association of Rheumatology Health Professionals annual meeting.

Paul Emery, MD, MA, FRCP, Arthritis Research UK Professor of Rheumatology, director of the Leeds Institute of Rheumatic and Musculoskeletal Medicine, and director of the Leeds Musculoskeletal Biomedical Research Centre at Leeds Teaching Hospitals Trust, sees the benefit in tapering biologic DMARDs.

During the session To Taper or Not to Taper? — Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity, Dr Emery said that tapering treatment was desirable, and possible, in patients with early stages of the disease, and even in some cases where the disease has already been established.

Dr Emery’s argument aligned with the EULAR recommendations that reducing the use of TNF inhibitors after achieving an optimal disease activity score of less than 2.6 is associated with beneficial outcomes. He also explained the benefit of tapering in conjunction with early treatment for these patients.

During the session, he recommended that patients should start treatment at the first signs of the disease, with the goal of reaching remission within 6 months, which offers the chance for tapering. Novel data about this could potentially change the future of disease management.

“You get the opportunity to de-bulk the disease and the opportunity then to forget about radiographic damage,” Dr Emery said. “But I make the point that at the moment the only remission data we have is from treating very severe patients. I would say that we’ve gotten it all wrong. We should be treating really mild patients to the level that nearly everyone can taper and the majority can actually stop therapy.”

Tapering biologic DMARDs would provide major cost benefits for both patients and payers. Treatment for 12 months in 90% of patients would only cost approximately one-quarter of what it costs to treat 20% of patients for 20 years, according to the session.

“So the unthinkable is that the first use of biologics could be cost-effective, and if the reason that we do it is that, I think that’s really good reason for tapering,” Dr Emery said.

Results from the OPTIMA study indicate that after 6 months of treatment cessation of adalimumab, only 10% of individuals had a flare-up. Data from additional studies show that 75% of patients will not flare up, which means that only 3% of patients will experience problems, according to the session.

“So you’re spending a lot of money for 3% complications,” Dr Emery said.

Arthur Kavanaugh, MD, Professor of Medicine and Director of the Center for Innovative Therapy, University of California, San Diego, took the opposite side during this debate and advocates for not tapering treatment.

While some patients with rheumatoid arthritis with limited disease activity will see benefits from tapering or stopping treatment with TNF inhibitors, some may not. According to the CORONA registry, which involved patients with limited disease activity who stopped treatment, patients almost always have a flare-up.

The average time to flare-up was 18 months, but 73% of patients went 2 years without a flare-up.

“You can interpret this data in several ways,” Dr Kavanaugh said. “The current theme, and one that’s going to have great importance to us practically, is that it’s really hard to know who’s going flare versus who’s going to have persistent benefit. It’s hard for us to pick that ahead of time.”

Each flare inflicts damage that can change the patient’s functionality, and could lead to a worse quality of life.

In the BeSt study, 8% of patients who underwent TNF inhibitor tapering did not respond well to treatment.

“So the data say sure, you can try this, but 8% of your patients were doing fine,” Dr Kavanaugh said. “You changed their therapy around, and now they never get back to where they were. Is that good or not so good?”

Dr Kavanaugh is also concerned with the lack of approaches to determine who would benefit from tapering. Although the HONOR study has tried to determine this, there has been no proven way to predict the benefit.

“That’s great for publications. It’s great for science, but it doesn’t help me in the clinic,” Dr Kavanaugh said. “I need something that’s very, very predictive before I’m going to take Mrs. Jones and say let’s cut back on your treatment.”

There are also concerns about how tapering may affect other aspects of the disease, such as cardiovascular health. While inflammation resulting from tapering would likely take a while to cause damage, it could potentially increase the risk of cardiovascular disease.

Dr Kavanaugh said that tapering is also an ethical discussion that could put the medical community in a dangerous spot, should tapering be adopted for financial reasons without fully knowing the consequences. He wrapped up his argument with a traditional Texas expression.

“Don’t poke a skunk. If you’re doing well, keep on treatment and keep doing well,” Dr Kavanaugh concluded.