A proof-of-concept trial suggests it’s possible to further reduce the risk of glucocorticoid toxicity.
A proof-of-concept study suggests that an eight-week taper of corticosteroids taken in combination with tocilizumab may be enough to induce and maintain remission in patients with giant cell arteritis.
The prospective, single-arm open-label trial conducted at Massachusetts General Hospital resulted in more than three-quarters of patients attaining sustained glucocorticoid-free remission at week 52.
“Furthermore, only 16% of the adverse events occurring during the treatment period were related or probably related to prednisone, and no cases of giant cell arteritis-related vision loss occurred during the study,” wrote the authors in the Lancet Rheumatology.
While noting that the research needs to be backed up by a controlled clinical trial before such a strategy case be recommended in clinical practice, the authors pointed to its potential benefits in preventing many of the complications associated with long-term glucocorticoid use.
The researchers, led by Harvard Medical School’s Dr Sebastian Unizony, recruited 30 patients aged at least 50 with new-onset or relapsing GCA.
They received 162mg tocilizumab per week for 52 weeks, and in addition received an eight-week prednisone taper with a starting dose based on clinical judgement as to the minimum dose required to achieve disease control. Patients who didn’t achieve remission, or relapsed after remission, were given another eight-week taper.
The primary outcome was sustained prednisone-free remission at week 52. Secondary endpoints included cumulative prednisone dose, glucocorticoid toxicity and patient-reported outcomes. Safety, as determined by adverse events and serious adverse events, was also recorded.
At week 52, 77% of patients were in sustained remission. Of the seven patients that relapsed, six received a second eight-week taper, of whom four regained and maintained remission for the rest of the trial.
The mean cumulative prednisone dose overall was 1197mg: the mean cumulative dose for responders was 1052mg and for non-responders was 1673mg.
By contrast, the 26-week steroid taper in the landmark 2017 GiACTA trial resulted in a mean cumulative steroid dose of around 1800mg, while the former mainstay of treatment, glucocorticoid monotherapy, resulted in doses of 5-12g over a period of 18-24 months.
“It is telling how far treatment of giant cell arteritis has moved since 2017: tocilizumab is now considered standard of care, and in this study, it was the 8-week glucocorticoid taper that was the experimental therapy being tested,” remarked Dr Sarah Mackie and Dr Rayna Bhogal of the University of Leeds in a linked comment.
While all 30 patients experienced at least one adverse event in the trial, only four experienced serious adverse events, including septic olecranon bursitis, diverticulitis, fragility fracture and cholecystitis.
“The most feared consequence of giant cell arteritis is permanent vision loss, which occurs in 10–20% of patients with newly diagnosed disease typically before or shortly after treatment with glucocorticoids is instituted,” wrote the study authors.
“In our study, none of the patients developed permanent vision loss by the end of the 56 weeks of follow-up despite 37% of them reporting giant cell arteritis-related visual manifestations at the study onset.”
The non-serious adverse events were consistent with the known safety profile of the drugs in GCA patients. Levels of glucocorticoid-related toxicity were also low.
“A randomised controlled trial is required to confirm these findings and formally assess the glucocorticoid-related toxicity associated with 8 weeks of prednisone in comparison with current standard-of-care glucocorticoid tapers,” the authors concluded.
