Biologic drugs make it possible for many people with inflammatory types of arthritis, such as rheumatoid arthritis (RA), to achieve low disease activity or remission. But because of the drugs’ cost and the potential for serious side effects, many patients don’t want to stay on them indefinitely, so researchers have been looking at whether it’s possible to taper or stop them. A new study, published recently in Arthritis & Rheumatology, is adding to the growing body of research on the topic.
The study found that RA patients with stable, low disease activity who stopped treatment with tumor necrosis factor inhibitors (anti-TNFs), a type of biologic, were about three times as likely to experience a disease flare in the following 12 months compared with those who continued using anti-TNFs. Among the 817 patients who had used an anti-TNF for at least one year, 51.2 percent who stopped therapy experienced a flare compared with 18.2 percent of those who continued, the study found. Those who stopped anti-TNF treatment were also almost three times more likely to be hospitalized – 6.4 percent versus 2.4 percent – compared with those who continued therapy.
Despite the three-fold higher risk of flares among patients who stopped taking an anti-TNF, the study authors write, “the finding that even among patients with established RA, almost one-half were able to stop their [anti-TNF] treatment could be considered a promising result.”
“Patients or rheumatologists may find a 50 percent chance for successful stopping to be worth a try, especially if they have complaints about TNF inhibitors,” says study author Marjan Ghiti Moghadam, MD, of the University of Twente in Enschede, Netherlands.
Good News or Bad?
Richard Brasington, MD, director of the rheumatology fellowship program at Washington University in St. Louis, says an increase in flares such as this is what one would expect in people stopping any effective treatment. “RA is a chronic disease like hypertension, diabetes or coronary disease,” he says. “You may be able to get the disease under control and cut back a little, but it is not like you can treat people and then stop the therapy. I really think the idea that you can treat people and then cut back on therapy is fallacious.”
On the other hand, Daniel Furst, MD, professor emeritus at UCLA, is more optimistic. “I think that attempting to decrease drugs in patients under good control is excellent and that this study supports the view that some patients can do that,” he says.
Identifying RA “Remission”
Kerry Wright, MD, a rheumatologist at Mayo Clinic in Rochester, Minn., says she has found flares to be common in patients who stop anti-TNF treatment. “The results are consistent with what we often see in clinical practice,” she says.
Dr. Wright and Dr. Furst say the rate of flares could be lower if a stricter definition of remission were used to determine which patients could stop treatment. In the study, stable, low disease activity or remission were defined primarily by DAS28 scores, a measure of disease activity based largely on the presence or lack of swelling and tenderness in 28 joints.
“We have recognized that patients may be asymptomatic and not have obviously swollen or tender joints on examination but may continue to have ongoing joint inflammation that is detectable only on imaging studies – MRI or ultrasound,” says Dr. Wright. “This may potentially account for the relapses that occur when treatment is withdrawn in patients who clinically appear to be in remission.”
Neither Dr. Brasington, Dr. Furst or Dr. Wright were involved in the study.
Other factors that could have affected the results include the longstanding nature of RA in the study population (12 years on average) – Dr. Furst says continued remission is more likely in people with early disease – and the way the patients stopped the drugs. The study doesn’t reveal whether they stopped them abruptly or gradually, Dr. Furst says.
A piece of good news from the study is that in people whose RA flared, resuming the anti-TNF brought the disease back into control in most cases. Of 195 patients who restarted anti-TNFs after a flare, almost 85 percent achieved either disease remission or low disease activity within 26 weeks of restarting the drugs. “Most of the time, if you stop [the anti-TNF] and begin to flare, you can be recaptured, so to speak,” says Dr. Furst.
Is It Worth the Risk?
Still rheumatologists are divided on the advisability of stopping anti-TNFs in their RA patients. In cases where patients ask to stop the drugs, which are expensive and must be injected or infused, Dr. Furst says tapering the drugs slowly and restarting at the first sign of disease activity is probably the best course of action. “I would either decrease the dose or spread out the doses – for example, every third week instead of every second week – and then at some point that is very variable, depending on the patient, I stop the drug and resume the drug if there are signs of increased disease,” he says.
Dr. Brasington, however, is more concerned about patients experiencing a flare. “People who have had their disease controlled need to stay on the medicine,” he says. The one exception, he says, is corticosteroids, which should be tapered due to the risk of side effects.
Dr. Wright takes a more moderate stance. “The important message of this study is that risk remains for flares of disease with discontinuation of [anti-TNFs] even in patients who clinically have stable disease,” she says. “This is an area that will need further study in order to determine if there are tools that will allow us to better predict circumstances that will allow safe discontinuation of TNF inhibitor treatment.”
Dr. Moghadam says, “This is a matter of shared decision making between doctor and patient.” She says her group is now working to find predictors of who can successfully stop anti-TNF therapy; their results should be published soon.
Author: Mary Anne Dunkin for the Arthritis Foundation