Tocilizumab-Methotrexate Synergy Offers Rapid RA Relief

Tocilizumab may boost methotrexate to achieve rapid suppression of inflammation and protection against disease progression in rheumatoid arthritis. Interim results of a multicenter Japanese study suggest that the addition of tocilizumab to methotrexate provides enhanced clinical efficacy and prevention of joint destruction over either agent alone.

The study appears in the Jan. 5 online issue of the Annals of Rheumatic Diseases.

The current push in rheumatoid arthritis management is early, aggressive treatment with the goal of remission. Methotrexate has been the gold standard, but it may not provide adequate therapeutic coverage in some patients or meet the new paradigm of rapid disease suppression. Tocilizumab has been shown to be more effective than methotrexate, but a team of Japanese researchers sought to learn whether the addition of tocilizumab to a methotrexate regimen provided benefit over a switch.  [[{"type":"media","view_mode":"media_crop","fid":"45051","attributes":{"alt":"@ImagePointFR/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_7127836646977","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5093","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":"@ImagePointFR/Shutterstock.com","typeof":"foaf:Image"}}]]

Led by Tsutomu Takeuchi, of the Keio University School of Medicine, the study reports findings from the first year of the two-year SURPRISE study (Success of Tocilizumab in RA Patients with Remission Induction and Sustained Efficacy after Discontinuation). It includes 223 patients between 20 and 75 years old who had moderate to severe rheumatoid arthritis despite methotrexate therapy.  A total of 118 patients were randomly selected to have tocilizumab added to their methotrexate regimen, and the remaining 115 were switched to tocilizumab.  Patients were followed for 52 weeks.

“The switch strategy was able to catch up later to the add-on protocol with respect to clinical efficacy, but the structural damage progressed more in a year with the switch therapy,” the study authors reported.

Although remission rates were the same at week 52 (72% for patients in the add-on group and 70% for those in the switch group), remission rates were 70% vs 55%, respectively, at week 24. Among patients with clinically relevant radiographic progression at week 52, the mean change in van der Heijde-modified total Sharp score (mTSS) was significantly greater in the switch group than the add-on group (9.0/year vs 5.0/year; P < .05).

The first-year of this two-year trial confirms earlier findings in showing that methotrexate plus tocilizumab provides superior, faster therapeutic benefit over tocilizumab alone. Limitations of the study:  It was not double blind and the sample size established to prove the inferiority of the switch to add-on strategy was not met. The second phase of the study will examine whether remission rates hold after discontinuation of the tocilizumab.  

References:

Kaneko Y, Atsumi T, Tanaka Y, et al. “Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate:  52-week results from a prospective, randomised, controlled study (SURPRISE study),” Annals of Rheumatic Diseases. Published online Jan.  5, 2016 as 10.1136/annrheumdis-2015-208426.  (http://dx.doi.org/10.1136/annrheumdis-2015-208426).

Jones G, Sebba A, Gu J, et al. “Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis:  the AMBITION study,” Annals of Rheumatic Diseases.  Jan 2010; 69(1):88-96. doi: 10.1136/ard.2008.105197.