Stopping Biologic Therapy in RA Could Trigger Flares

February 22, 2016

While there are many studies that examine how well TNFi biologic therapies work in rheumatoid arthritis, few studies have examined when TNFi can be safely stopped, until now.

While there are many studies that examine the effectiveness of TNFi biologic therapies to treat rheumatoid arthritis, few studies have examined the point at which TNFi therapy be safely stopped while still achieving disease remission.

Now, a study published in the Feb. 11 issue of Arthritis and Rheumatologyshows that stopping TNFi (tumor necrosis factor inhibitors) therapy in patients who are in remission or in stable low disease activity, can lead to more than a threefold risk of developing a flare within one year of stopping therapy.

TNFi therapy is generally prescribed  when patients fail to respond to DMARDs  alone or as a combination treatment. But it remains unclear if patients in remission or in stable low disease activity need to continue taking TNFi or stop treatment altogether. Some smaller studies have shown that it is possible to discontinue TNFi therapy in patients in remission or stable low disease activity, but it is unclear if it can be safely restarted if needed. Other small studies show that in 25-60 percent of rheumatoid arthritis patients on combination methotrexate-TNFi therapy retain low disease activity after stopping TNFi therapy.

TNFi therapy can be associated with some serious risks, such as cancer and infections, plus - they are expensive.  In some cases, the researchers wrote, patients are kept on TNFi therapy indefinitely.

The study, a pragmatic multicenter open-label randomized controlled trial of 817 patients, included two groups of patients. The first group of 531 patients stopped TNFi  after achieving remission or stable low disease status. While the second group of 286 patients continued TNFi therapy.[[{"type":"media","view_mode":"media_crop","fid":"46144","attributes":{"alt":"©SebastianKaulitzki/Shuttersstock.com","class":"media-image media-image-right","id":"media_crop_688001518137","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5340","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©SebastianKaulitzki/Shuttersstock.com","typeof":"foaf:Image"}}]]

For most of the patients, this was their first course of TNFi therapy, which was primarily adalimumab (49.0%) or etanercept (42.4%).  Approximately 80 percent, or 653 patients in the study, were in remission (DAS28 <2.6).

Within six months, 213 out of 531 (40.1%) patients in the stop group experienced a flare as compared to 34 out of 286 (11.9%) patients in the continuation group. And, within 12 months, 272 out of 531 (51.2%) patients in the stop group experienced a flare as compared to 52 out of 286 (18.2%) in the continuation group.

Some of the patients restarted therapy after experiencing flare-ups:  252 of 531 patients (47.5%) in the stop group restarted TNFi after flares, and of 195 patients who restarted within 26 weeks, 132 (67.7%) achieved clinical remission and an additional 33 (16.9) regained low disease activity within 26 weeks.

There were more hospitalizations in the stop group than in the continuation group (6.4% vs 2.4%).

Led by Marjan Ghiti Moghadam, M.D., of the University of Twente in The Netherlands, the researchers caution that at 12 months, the study may have been too short to examine the long-term effects of stopping TNFi therapy.

 

References:

Marjan Ghiti Moghadam, Harald E. Vonkeman, et. al.

"Stopping Tumor Necrosis Factor-inhibitors in Patients with Established Rheumatoid Arthritis in Remission or Stable Low Disease Activity: A Pragmatic Randomized Multicenter Open-Label Controlled Trial,"

Arthritis and Rheumatology

. DOI 10.1002/art.39626 Accepted manuscript online Feb. 11, 2016.