A new paper from Boston highlights outcome research limitations beyond one year.
Researchers from Massachusetts General Hospital set out to investigate the outcomes of outcomes for patients with giant cell arteritis (GCA) treated with tocilizumab.
With limited therapeutic options and a strong reliance on corticosteroids, GCA patients face the prospect of disease relapse and corticoid toxicity.
While there are some promising steroid-sparing treatments on the horizon, the study authors point out that tocilizumab is the only medication with a proven record of efficacy in terms of remission maintenance, steroid-sparing and health-related quality of life when taken for one year by patients with new-onset and relapsing GCA.
At this stage, though, the optimal duration of treatment is unclear.
“To our knowledge, this is the first study to report detailed real-world data on the outcomes in patients treated with long-term TCZ and specifically address the effects of TCZ treatment duration on the risk of relapse and the incidence of relapse after discontinuation of TCZ courses longer than 12 months,” wrote the authors, led by rheumatologist Dr Mark Matza.
The aim of the research, which was published in RMD Open, was to evaluate efficacy and safety of long-term tocilizumab use, the rate of relapse after treatment discontinuation and how treatment duration affects risk of relapse.
The researchers conducted a retrospective analysis of the medical records of 65 patients treated with tocilizumab for at least nine months at the Massachusetts General Hospital. Patients with newly diagnosed or relapsed GCA, despite the use of glucocorticoids, were treated with tocilizumab at the discretion of their rheumatologist.
Of the 65 patients, two thirds were female, and the mean age was around 71 years. Most (59%) started tocilizumab after disease relapse, while 41% were newly diagnosed. All were taking prednisone upon tocilizumab initiation. Mean follow-up was around 3 years, and the primary outcome was disease relapse.
On average, patients took tocilizumab for almost two years. Those who discontinued it, due to long-term remission or adverse events, did so after a mean of 1.6 years.
Relapse rates during treatment were 15% for patients on their first tocilizumab course and 22% when all courses were considered for each patient. Among the patients who discontinued treatment, more than 40% relapsed. Longer courses of tocilizumab were less likely to result in relapse than shorter courses.
“Further research is needed to identify those individuals at greater risk of relapse after early TCZ discontinuation to maintain therapy beyond 12 months and to investigate whether a step-down strategy reducing the dose of TCZ prior to treatment withdrawal could improve the outcomes after therapy cessation,” suggested the authors.
Patients were taking a mean daily prednisone dose of 33.9mg when tocilizumab was initiated and were down to an average of 2.6mg at the end of follow up, with more than three quarters of patients completely weaned off the steroid.
Around three quarters of patients experienced at least one adverse event, with 14% of patients experiencing serious adverse events over the follow-up period. These were consistent with the known safety profiles for these medications. Encouragingly, the rate of adverse events related to tocilizumab decreased over time.
Limitations of the study include potential bias arising from missing data, due to the retrospective data collection. And when the data was initially collected, in 2010, vascular imaging was rarely used, unlike today where it’s widely recommended. This limited the assessments that could be used in the analysis.
In conclusion, wrote the authors, “The optimal duration of TCZ treatment for patients with GCA has not been defined, and limited data are available regarding the efficacy and safety of long-term TCZ use in this patient population.
“Our results suggest that TCZ treatment beyond 12 months is efficacious in maintaining disease remission and sparing glucocorticoid use in most patients, with a long-term safety profile consistent with that observed with TCZ for other indications.
“These results could aid clinical decision making when discussing with GCA patients the risks and benefits of continuation vs discontinuation of TCZ after 12 months of treatment.”
