Low Disease Activity May Indicate Time to Stop Biologics

March 27, 2017

Physicians should weigh the risks and benefits of adalimumab discontinuation in rheumatoid arthritis patients who achieve low disease activity, researchers report.

Researchers in Japan found that approximately 80% of rheumatoid arthritis patients who discontinued adalimumab after achieving low disease activity with methotrexate plus adalimumab did not have flares for three years.

The study appears in the March 14 issue of Arthritis Research & Therapy.

HOPEFUL-3 was a 104-week observational study of 172 Japanese patients with early rheumatoid arthritis who were part of the HOPEFUL-1 and HOPEFUL-2 studies. Patients who completed a 1-year observational period of HOPEFUL-2 without receiving a biological agent other than adalimumab and who provided informed consent to participate in HOPEFUL-3 were enrolled in the study.  Approximately 79 patients received adalimumab plus methotrexate (adalimumab continuation group) and 93 patients received methotrexate alone (adalimumab discontinuation group). This study was conducted between February 2011 and June 2014.

Led by Yoshiya Tanaka, M.D., from University of Occupational and Environmental Health in Japan, the goal of the study was to investigate whether patients who achieved low disease activity would be in low disease at 3 years after discontinuation of adalimumab. The primary outcomes were changes in the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) and the proportion of patients who achieved low disease activity (DAS28-CRP < 3.2) at week 208.

Approximately 80%, or 59 of the 74 patients, in the adalimumab discontinuation group were still in low disease activity at week 208 and had fewer adverse events compared with those who continued with adalimumab. Moreover, the proportion of patients who achieved clinical remission in the adalimumab discontinuation group was significantly lower at week 208 compared to the adalimumab continuation group (65% vs. 89%, respectively, p = 0.001).

There were no cases of tuberculosis or deaths during the study period. The proportion of patients who experienced adverse events was significantly lower in the adalimumab discontinuation group than in the adalimumab continuation group (9.7% vs. 32.9%, respectively; p < 0.001). In the adalimumab continuation group, serious adverse included bronchiolitis, urinary tract stone, ascites fluid, and hepatic cirrhosis. In the adalimumab discontinuation group, one patient had serious interstitial lung disease.

Rheumatoid arthritis is an inflammatory disease that can lead to destruction of the joints and cause functional disability for patients. Treatments for rheumatoid arthritis have improved over the years with the introduction of biological agents such like tumor necrosis factor inhibitors. Previous studies have shown than tumor necrosis factor inhibitors combined with methotrexate achieve better outcomes in patients than treatment with methotrexate therapy alone.

Although recent studies have examined the feasibility of discontinuing the use of biological agents in patients who have achieved low disease activity, the effects of this strategy have not been evaluated on a long-term basis with regard to disease activity and safety.

“The results of this 104-week follow-up study indicated that approximately 80% of the Japanese patients with early RA were in LDA after 3 years ADA discontinuation,” wrote Tanaka and colleagues. “In addition to the safety benefits for patients with RA, discontinuation of biological agents after achievement of LDA or remission may also benefit the healthcare system by reducing the economic burden associated with the long-term use of biological agents.”

Limitations

Among the limitations associated with this study, included the observational nature of the study. And, patients were not randomly assigned to treatment groups.

“The results of this study were not conclusive, but they suggest that long-term discontinuation of adalimumab treatment might be a feasible and beneficial therapeutic option for patients with early rheumatoid arthritis who achieved low disease activity,” the authors wrote.

Disclosures:

Funding

This study was funded by AbbVie GK and Eisai Co., Ltd.

Disclosures

YT has received consulting fees, speaking fees, and/or honoraria from AbbVie, Chugai, Daiichi-Sankyo, Bristol-Myers Squibb, Mitsubishi Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi Kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, and GlaxoSmithKline and has received research grants from Mitsubishi Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers Squibb, MSD, Astellas,

AbbVie, and Eisai. HY has received research grants from AbbVie GK, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and UCB; has received consulting fees from AbbVie GK, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and UCB; and has received speaker’s bureau fees from AbbVie GK, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and

UCB. NI has received research grants from Abbott Japan, Astellas, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda and has received speaker’s bureau fees from AbbVie GK, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and UCB. NM has received research grants from AbbVie, Astellas, Banyu, Chugai, Daiichi

Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Takeda, and Teijin. KK, JK, and NA may own stock/stock options in AbbVie GK and are full-time employees of AbbVie GK. TT has received research grants from AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer, Sanofi, Santen, Takeda, and Teijin; has received consulting fees from AstraZeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, and Asahi

Kasei Medical; and has received speaker’s bureau fees from AbbVie, Bristol-Myers Squibb, Chugai, Eisai, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda.

References:

Yoshiya Tanaka, Hisashi Yamanaka, Naoki Ishiguro, et al. “Low disease activity for up to 3 years after adalimumab discontinuation in patients with early rheumatoid arthritis: 2-year results of the HOPEFUL-3 Study,” Arthritis Research & Therapy. Published March 14, 2017. DOI: 10.1186/s13075-017-1264-6.