May 20, 2019
2 min read

Increasing tocilizumab dose interval reduces chance of maintaining remission in RA

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Increasing the dose interval of subcutaneous tocilizumab is associated with a lower chance of maintaining remission after 24 weeks, and is not linked to improved tolerability, among patients with rheumatoid arthritis, according to data published in Arthritis & Rheumatology.

“[Tocilizumab] was initially developed as an intravenous formulation, but a subcutaneous formulation was recently developed, with a clinical efficacy and safety similar to intravenous [tocilizumab],” Raimon Sanmarti, MD, PhD, of the Rheumatology Service Hospital Clinic of Barcelona, and colleagues wrote. “A retrospective study suggested the possibility of dose reduction for intravenous [tocilizumab] in a substantial proportion of RA patients without a disease flare. However, the efficacy and safety of a dose reduction of [tocilizumab] have not been evaluated in randomized controlled trials for either the intravenous or subcutaneous administration route.”

To determine the safety and efficacy of increasing dose intervals of subcutaneous tocilizumab (Actemra, Genentech) among patients who had achieved clinical remission in RA, Sanmarti and colleagues performed a randomized, open-label trial, as part of the international TOZURA project.

This larger project includes 11 studies in 22 countries, and was designed as a single-arm study aimed at evaluating the efficacy and safety of weekly, 162-mg doses of subcutaneous tocilizumab, alone or in combination with conventional synthetic disease-modifying antirheumatic drugs, for 24 weeks in patients with moderate-to-severe RA who failed to respond to TNF inhibitors or conventional synthetic DMARDs.

Sanmarti and colleagues conducted a continuation of this single-arm study. Their study was conducted in 46 sites across Spain, Ireland and Portugal between September 2013 and March 2016. They recruited the 179 participants who had achieved clinical remission in the previous single-arm study, and randomly selected 90 to increase their tocilizumab dose interval to every 2 weeks, while the remaining 89 continued their weekly regimen, for an additional 24 weeks. Clinical remission was defined as a DAS28 score of less than 2.6.

According to the researchers, 90% of participants who continued their initial regimen remained in clinical remission at week 48, compared with 73% among patients who increased their dosing interval (P = .004). In addition, although various other efficacy measures appeared to favor the initial regimen, such results lacked statistical significance, save for mean change in DAS28 from baseline to week 48. Tolerability and safety were similar between the two groups.

“Reducing the dose of [subcutaneous tocilizumab] to 162 mg every two weeks in patients who achieved sustained remission at the recommended dose of 162 mg once a week was associated with a lower likelihood of maintaining remission after 24 weeks when compared to continuing with the standard regimen of this agent and was not associated with better tolerability,” Sanmarti and colleagues wrote.


They added, “However, most patients did remain in remission with a half-dose of subcutaneous tocilizumab, and this strategy therefore warrants further investigation in randomized controlled trials with longer follow-up periods and a comparison between a continuation strategy and a strategy that includes dose reduction and restarting of full doses in cases of relapse.” – by Jason Laday

Disclosure s : Sanmarti reports research grants from Bristol-Meyers Squibb, MSD and Pfizer, as well as consulting fees from AbbVie, Eli Lilly, Roche, Sanofi and UCB. Please see the full study for additional author disclosures.