A recent phase 2 safety and efficacy study of an anti-interleukin-17A monoclonal antibody for the treatment of giant cell arteritis patients suggests there may soon be another alternative to glucocorticoid treatments.
The results of the TitAIN (“TITAN”) study, recently published in Lancet Rheumatology,[1] show that patients with active giant cell arteritis treated with the anti-interleukin-17A monoclonal antibody secukinumab had a higher sustained remission rate than patients in a placebo group. The antibody therapy was tolerated well, supporting the development of secukinumab as a treatment for people with giant cell arteritis.
It is estimated that 1 in every 2000 people over the age of 50 has giant cell arteritis, an inflammatory disease of blood vessels. The symptoms can include new headaches, scalp tenderness, jaw pain with movement, vision problems, fever, weight loss, fatigue, and shoulder pain. It is crucial to diagnose and start treatment immediately when giant cell arteritis is suspected in order to prevent complications such as permanent vision loss and other blood vessel issues.
High doses of glucocorticoids are currently the standard of care for giant cell arteritis. Although these drugs reduce inflammation effectively, some patients either do not respond fully to the treatment or their symptoms return after the steroids are tapered. In addition, long-term steroid use raises the risks of diabetes, osteoporosis, atherosclerosis and a plethora of other toxicities.
For those patients who do not respond to steroids, tocilizumab, the interleukin-6 receptor blocker is the only biologic treatment currently approved by the European and U.S. health authorities for giant cell arteritis. While this antibody treatment can help reduce the amount of steroids needed, many patients still do not achieve long-term remission of their symptoms.
In the trial of secukinumab, 11 clinics across Germany enrolled a total of 52 patients in a randomized, parallel-group, double-blind placebo-controlled study. All patients had active disease and were already receiving glucocorticoids with a prednisolone equivalent dose of 25–60 mg/day.
Patients enrolled in the trial followed a 26-week glucocorticoid taper, similar to other phase 2 clinical trials. Seventy percent of patients in the secukinumab group remained in sustained remission until week 28, compared with twenty percent of patients in the placebo group – encouraging findings that justify the pursuit of a phase 3 trial.
TitAIN used the Steritas Glucocorticoid Toxicity Index (GTI) as an exploratory outcome in the trial.[2] The GTI data were consistent with a reduction of steroid-toxicity by secukinumab, supporting the use of the GTI in future phase 3 trials.
The GTI scores suggested lower glucocorticoid toxicity in the secukinumab group at week 52, both in analyses that included all trial subjects (intention-to-treat) as well as those limited to subjects who completed the trial. Tests of statistical significance were not performed because of the exploratory nature of the endpoint.
Commenting on the results, John H. Stone, MD MPH, Professor of Medicine at Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital, stated:
"These results are very encouraging with regard to the efficacy of secukinumab and the ability of this medication to exert important effects on the reduction of steroid-toxicity. Such an impact is critical for this disease that tends to affect elderly individuals, who already have such a high risk of toxicity from glucocorticoids.”