RA remission maintained after Actemra discontinuation
Among patients with rheumatoid arthritis who achieved remission after they were treated with either tocilizumab monotherapy or in combination with methotrexate, low disease activity was maintained following tocilizumab discontinuation in more than half of individuals, according to findings published in the Annals of the Rheumatic Diseases.
The researchers also found that tocilizumab retreatment led to remission in more than 90% of patients.
“Recently, there have been rigorous attempts, from the risk–benefit point of view, to identify whether the discontinuation of biologic agents is possible in patients who have achieved remission or low disease activity,” Yuko Kaneko, MD, PhD, of the Keio University School of Medicine, and colleagues wrote. “Accumulated evidence has shown that 0% to 59% of patients treated with methotrexate and TNF inhibitors can successfully remain in remission or low disease activity after discontinuing TNF inhibitors. ... Compared with TNF inhibitors, little is known regarding tocilizumab-free remission or low disease activity.”
To analyze sustained remission following the discontinuation of tocilizumab (Actemra, Genentech) in patients with RA who were treated with the drug alone or in combination with methotrexate, the researchers followed participants from a previous study in Japan testing the efficacy and safety both treatment strategies. The SURPRISE study, a 2-year, open-label randomized controlled trial, enrolled 233 patients with RA, and randomly assigned them to either add tocilizumab to their current methotrexate regimen or switch from methotrexate to tocilizumab.
In the first year of the study, researchers compared the efficacy and safety of the two treatment groups. For their own study, representing the second year of the SURPRISE trial, Kaneko and colleagues followed 102 participants who achieved remission during the first year and agreed to discontinue tocilizumab. This group included 49 patients from the combination therapy group, who were then treated with methotrexate alone following tocilizumab discontinuation, and 53 from the monotherapy cohort, who after discontinuation received no disease-modifying antirheumatic drugs during the second year of the study. Endpoints included tocilizumab-free remission and low disease activity rates, functional outcome, radiological outcomes evaluated with the modified total Sharp score and safety.
The researchers also studied the efficacy of reinstituted tocilizumab or methotrexate. They added tocilizumab to methotrexate in 16 patients in the combination therapy group due to flares between weeks 52 and 104. In the monotherapy group, 35 patients restarted either methotrexate, tocilizumab or both.
According to the researchers, sustained low-disease activity rates — based on the DAS28 — were 55% for patients who initially received tocilizumab and methotrexate combination therapy in the first year, and were then treated with methotrexate alone following discontinuation in the second year (P = .005). For those initially treated with tocilizumab alone and later received no DMARDs following discontinuation, the rate was 27% (P = .005). In addition, sustained remission rates at the end of year 2 were 24% for the combination therapy group and 14% for the monotherapy group (P = .29). The researchers also found that radiological progress was comparable between the two groups. They also noted that restarting tocilizumab induced remission in all but two patients after 36 weeks.
“Our study has proved that more than half of patients would remain in low disease activity after discontinuing tocilizumab with continued methotrexate,” Tsutomu Takeuchi, MD, PhD, a professor of rheumatology at the Keio University School of Medicine and one of the researchers, told Healio Rheumatology. “It is a new, relevant finding because tocilizumab has been believed to be difficult to stop without csDMARDs. Stopping tocilizumab would be a good approach, especially from medical economics point of view. What kinds of patients can stop tocilizumab remaining in remission, and whether stopping methotrexate with continued tocilizumab is feasible are other clinical questions to be solved.” – by Jason Laday
Disclosure: Kaneko reports grants or speaking fees from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi and UCB. Takeuchi reports research grants or speaking fees from Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, Teijin Pharma, AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma, Astra Zeneca KK, Eli Lilly Japan KK, Novartis Pharma KK, AbbVie GK, Nipponkayaku, Janssen, Pharmaceutical KK, Taiho Pharmaceutical and Pfizer Japan. Please see the study for all other authors’ relevant financial disclosures.