Tocilizumab taper increases time to relapse vs. abrupt withdrawal in giant cell arteritis
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Key takeaways:
- Patients who abruptly discontinued tocilizumab had significantly shorter time to relapse than those who tapered.
- Adverse events led to discontinuation in 15% of patients.
Tapering tocilizumab leads to a longer relapse-free period in patients with giant cell arteritis, compared with abrupt discontinuation, according to data published in Seminars in Arthritis and Rheumatism.
“Tocilizumab (TCZ), a monoclonal antibody against IL-6 receptors, has been approved as a therapeutic agent for GCA based on the results of two randomized controlled trials,” Marc K. Nielsen, of the department of rheumatology at Aarhus University Hospital, in Denmark, and colleagues wrote. “However, the effectiveness and safety of TCZ in routine care has only scarcely been described. In addition, follow-up data has revealed a high relapse frequency after abrupt withdrawal of TCZ treatment. Consequently, the ideal strategy for treatment discontinuation, including the potential of tapering, remains to be established.
“Another challenge linked to tapering glucocorticoids in GCA patients is that some individuals may be more susceptible to relapse,” they added. “Consequently, several risk factors for GCA relapse have been described in glucocorticoid-treated GCA patients, including large-vessel GCA (LV-GCA). However, these risk factors remain to be investigated in TCZ-treated patients.”
To compare relapse incidence among patients with GCA who taper tocilizumab (Actemra, Genentech) vs. those who abruptly discontinue the drug, Nielsen and colleagues conducted a retrospective cohort study of individuals treated at the Aarhus University Hospital between January 2012 and Aug. 15, 2022. The analysis included 155 patients (median age at diagnosis, 69 years) treated with tocilizumab for GCA, 57 of whom tapered off and 59 of whom abruptly withdrew.
Initial tocilizumab doses were either given intravenously every 4 weeks or subcutaneously weekly or every second week. For tapering, the dosage was administered either every second week or every third week. Participants were followed until meeting one of five endpoints: tocilizumab discontinuation due to insufficient response; discontinuation due to relapse, or first relapse after discontinuation; death; or end of the follow-up period. The researchers used Kaplan-Meier curves to estimate relapse-free survival, and a Wilcoxon-Brewlos-Gehan test to compare tapering and abrupt discontinuation.
Of all patients who discontinued tocilizumab, 40% (n = 42) relapsed within the first year, according to the researchers. Those who abruptly discontinued demonstrated significantly shorter time to relapse than all tapering patients (P = .02), as well as those patients who tapered from weekly treatment to every second week (P < .01).
Among those who tapered, 38 tapered to every second week and 19 tapered to every third week. Relapses in those groups totaled six (16%) and two (11%), respectively. Of the 59 patients who abruptly discontinued, 27 (46%) relapsed during follow-up, according to the researchers.
Adverse events — most frequently neutropenia and infections — led to discontinuation for 15% of patients over a median time of 279 days (IQR 142-484) from treatment initiation.
“This is the first study to investigate the relapse frequency after TCZ discontinuation in patients with GCA, comparing TCZ tapering with abrupt discontinuation,” Nielsen and colleagues wrote. “Tapering displayed an advantage over abrupt discontinuation in preventing relapses, suggesting tapering as a potential strategy for future management.
“In addition, this study emphasizes that the prevalence of adverse events was considerably higher compared to the studies that led to the approval of TCZ treatment,” they added. “Therefore, the risk of adverse events must consistently be taken into consideration prior to TCZ treatment in this elderly population.”
Perspective
Back to TopGiant cell arteritis treatment has changed in the last decade with the approval of tocilizumab. However, with new treatments there are always new questions, particularly after real world experience is gained.
The American College of Rheumatology’s and EULAR’s guidelines differ regarding when tocilizumab should be initiated for GCA. One thing that I found interesting about this study is that there was a median time of 206 days after diagnosis before tocilizumab was started, with relapse being the primary reason for initiation.
Another interesting difference is that patients using subcutaneous tocilizumab were dosed weekly or every second week. This raises the question of how this information would translate to patients who receive tocilizumab at diagnosis, per ACR guidelines, instead of after relapse. Also, would there be a different outcome if dosing was done weekly for all patients vs. every other week?
With the ever-changing treatment landscape of GCA and other rheumatologic conditions, ongoing studies are needed to make sure that we are providing the best treatment possible for our patients.
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