Biologic drugs make it possible for many people with inflammatory types of arthritis, such asrheumatoid 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 inArthritis & 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.
其他可能影响结果的因素包括研究人群中风湿性关节炎的长期性(平均12年)——弗斯特博士说，持续缓解更有可能发生在早期疾病的人——以及患者停药的方式。弗斯特博士说，这项研究并没有揭示他们是突然停用还是逐渐停用。
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.
赖特博士的立场更为温和。她说:“这项研究的重要信息是，即使在临床疾病稳定的患者中，停用[抗肿瘤坏死因子]仍有爆发疾病的风险。”“这是一个需要进一步研究的领域，以确定是否有工具可以让我们更好地预测情况，从而允许安全停用TNF抑制剂治疗。”
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