Phase II success for the IL-17A inhibitor has paved the way for a phase III trial.
A proof-of-concept phase II trial of secukinumab in patients with giant cell arteritis (GCA) has reported higher rates of remission and longer time to flare over 52 weeks compared with placebo, paving the way to a phase III trial.
The randomised, parallel-group, double-blind, multi-centre trial, TitAIN, included 52 patients aged 50 and over with new onset or relapsing GCA who were biologic naïve.
Participants were allocated 1:1 to 300mg secukinumab or placebo once a week for 4 weeks then every 4 weeks thereafter for 52 weeks. Patients in both groups underwent a 26-week glucocorticoid taper.
The primary endpoint was proportion of patients who achieved sustained remission at week 28, with secondary endpoints including proportion of patients in remission at week 52, time to first flare after remission and total cumulative prednisolone dose from weeks 28 to 52.
The researchers conducted a Bayesian analysis for the primary endpoint, with placebo results from the GCA tocilizumab trial (GiACTA) used as an informative prior for the TitAIN placebo group.
The results were presented at ACR 2021 and EULAR 2022, and have now been published in full in the Lancet Rheumatology.
A greater proportion of patients receiving secukinumab reached sustained remission at 28 weeks (70%) than those on placebo (20%), although by 52 weeks, remission rates had dropped to 59% and 8%, respectively. These results are similar to those in the GiACTA trial at 52 weeks (56% remission in the tocilizumab group vs 14% in the placebo group with 26-week prednisone taper).
The treatment group also had a longer time to first GCA flare, and there were no new or unexpected safety signals identified with secukinumab.
“In conclusion, secukinumab met the predefine criteria for proceeding to a phase 3 trial and showed higher sustained remission rates and a longer time to first giant cell arteritis flare than did the placebo over 52 weeks, thus supporting the development of secukinumab as a potential treatment for patients with giant cell arteritis,” wrote the authors.
“The safety profile of secukinumab in patients with giant cell arteritis was consistent with previous reports in patients with other inflammatory conditions, with no new or unexpected safety signals identified,” they added.
The phase III trial is currently recruiting.
In an accompanying comment, Dr Thurkka Rajeswaran and Dr Sarah Mackie welcomed the potential addition of secukinumab to the anti-GCA armamentarium, but said that clinicians should be cautious about what the TitAIN results mean for their practice.
“Although this Bayesian approach was sufficient to meet the sponsor’s prespecified criteria to proceed to a phase 3 trial, it relies on an assumption that data from a placebo group from the pre-tocilizumab era is just as applicable now in the post-tocilizumab era; however, practice has probably evolved considerably since that time,” they wrote.
“This study alone is clearly not yet adequate evidence that clinicians should prescribe secukinumab for patients with giant cell arteritis, and the results of the phase 3 trial are awaited.”
Meanwhile, findings of a large Italian observational study, published in the Annals of the Rheumatic Diseases, indicate that GCA phenotype varies by age.
Around 1000 people were grouped by age at disease diagnosis and followed up for two to seven years (median four years). The primary endpoint was the association of age at disease onset with the number of relapses.
“Our study shows that age at disease onset has a significant impact on the type of clinical manifestations, risk for ischaemic sequelae, treatment strategies, disease-related and treatment-related complications in patients with GCA,” wrote the authors.
Patients in the youngest group (aged ≤64 years at diagnosis) were more likely to have large-vessel GCA than those in other groups, and systemic symptoms at onset were more likely at a younger age, especially fatigue, fever and night sweats. However, they were less likely to have cranial symptoms (headache, scalp tenderness, jaw claudication and amaurosis fugax) and risk of serious infections than those in the older groups.
Those in the oldest group (≥80 years at diagnosis) had more ischaemic complications and risk of blindness than the younger groups. They were also taking fewer immunosuppressant medicines, indicating potential undertreatment.
Patients in the older group had more than double the risk of aortic aneurysm or dissection than that of patients aged 65-79.
Relapses were unaffected by age, as was the time to reach a low-dose glucocorticoid (≤5mg/day).
“In conclusion,” wrote the authors, “our study demonstrates that, given the higher risk for severe ischaemic manifestations, aortic complications, serious infections, death, and potential undertreatment, elderly patients with GCA represent a unique and challenging subgroup of patients that deserves further dedicated research to optimise their management and improve prognosis.”
