“ Biologic DMARDs (bDMARDs) are highly effective drugs for the treatment of RA, and the proportion of patients with RA in remission has risen since these medications became available,” explains Diego Kyburz, MD. “However, once in remission, patients often seek to decrease or discontinue their medication. As bDMARDs are costly, there is also an economic factor behind decreasing the dosage. It is, therefore, important to know whether bDMARDs can be decreased or discontinued, and in which patients, while avoiding the risk of a disease flare.”

Although randomized controlled trials have shown that bDMARDs can be successfully tapered or stopped in a significant proportion of patients with RA in remission, these studies usually have a relatively short observation period, Dr. Kyburz notes. “Although some associations have been reported, there is still a lack of information allowing for selection of patients who have a greater chance of maintaining remission after discontinuing bDMARD therapy,” he adds.

Majority Lost Remission Within 1 Year After Stopping bDMARDs

For a paper published in Rheumatology (Oxford), Dr. Kyburz and colleagues set out to identify predictors for maintenance of remission after bDMARD discontinuation. The researchers used data from a prospective cohort of patients with RA and included those in remission who had discontinued their bDMARD therapy. The primary outcome was time in remission after bDMARD discontinuation. Using Cox regression analysis, they searched for factors independently associated with time in remission.

The study team followed 318 patients with RA in bDMARD-free remission between 1997 and 2017. Of these, 74% were women, with a median age of 58, median disease duration of 7.5 years, and median observation time of 2.8 years. At the moment of bDMARD withdrawal, 59% of patients had concomitant treatment with methotrexate or leflunomide; 46% were treated with methotrexate and/or leflunomide during the entire bDMARD-free remission, whereas 36% never received methotrexate or leflunomide during bDMARD-free remission.

“Importantly, we found that a large majority (76%) of patients lost remission after bDMARD discontinuation within 1 year,” says Dr. Kyburz. “This indicates that most patients do need continuous therapy with bDMARDs to control RA disease activity.”

Disease Duration & Risk of Remission Loss Linked

Dr. Kyburz and colleagues found that patients with a longer disease duration (greater than 4 years) and those who did not meet Clinical Disease Activity Index (CDAI) remission criteria at baseline had a higher risk for loss of remission. On the contrary, patients with concomitant therapy with methotrexate or leflunomide had a decreased risk of remission loss (Figure).

“Our findings confirm and extend previous results from randomized controlled studies and suggest that bDMARD discontinuation should be considered primarily in patients with a disease duration of less than 4 years, who have fulfilled CDAI remission criteria, and patients should continue conventional DMARD therapy,” Dr. Kyburz says. “The research also suggests that when discontinuation of a bDMARD is being considered, rheumatologists should inform their patients that the risk for disease flare is high.”

Dr. Kyburz and colleagues would like to see further research in several areas. “For instance, are there differences between drugs/drug classes— such as TNF inhibitors versus IL-6R inhibitors or JAK inhibitors—in terms of maintenance of remission after discontinuation? Do the predictors for maintenance of remission differ between drug types?” Dr. Kyburz asks, rhetorically. “What are predictors for maintenance of remission in patients who stopped all DMARDs? Further research should also include information about biomarkers for a more refined prediction of a successful bDMARD discontinuation.”