New phase 3 data from the GCAptAIN trial show that secukinumab enabled a shorter steroid taper, less exposure, and meaningfully lower steroid-toxicity in giant cell arteritis (GCA). Although the trial did not meet its primary remission endpoint, the Glucocorticoid Toxicity Index (GTI), a secondary endpoint in the trial, quantified reductions in toxicity across nine health domains, delivering the evidence that cumulative dose alone cannot provide.[1]
GCA is the most common form of vasculitis in adults, affecting a population that is already at elevated risk of steroid-toxicity before treatment begins. Steroids remain the mainstay of GCA management, yet the condition is characterized by frequent relapse, prolonged exposure, and a cycle of toxicity accumulation that erodes quality of life in an already vulnerable group.
The GCAptAIN trial was led by John H. Stone, MD MPH, Professor of Medicine at Harvard Medical School and the Edward A. Fox Chair in Medicine at Massachusetts General Hospital and spanned 27 countries. The trial set out to determine whether secukinumab, a fully human monoclonal antibody targeting interleukin-17A, could improve outcomes for patients with GCA when added to a 26-week steroid taper. The results are more instructive than a binary pass/fail verdict would suggest.
The trial design and primary outcome
GCAptAIN (NCT04930094) was a randomized, double-blind, placebo-controlled phase 3 trial enrolling 354 patients with new-onset or relapsing GCA. Patients received secukinumab 300 mg (SEC-300), secukinumab 150 mg (SEC-150), each with a 26-week steroid taper, or placebo with a 52-week steroid taper. The primary endpoint was sustained remission at week 52.
The trial did not meet its primary endpoint, with sustained remission being achieved in 25.6% of SEC-300 patients versus 16.9% in the placebo arm (P=0.09).
The investigators are candid about contributing factors. The placebo arm received a 52-week taper versus 26 weeks for the secukinumab arms, a design asymmetry that likely blunted the ability to detect a statistically significant efficacy difference. A chance imbalance in sex distribution across treatment arms (SEC-300 was 72.1% female versus 56.0% for placebo) added further heterogeneity. A post hoc analysis adjusting for sex increased the marginal difference between SEC-300 and placebo to 10.9 percentage points, and in the female subgroup alone, sustained remission was 23.8% with SEC-300 versus 6.3% with placebo.
What the GTI revealed
Here is where the data becomes clinically significant in a way that the primary endpoint alone cannot capture.
Patients in the SEC-300 arm received a mean cumulative steroid dose of 3,158 mg versus 3,941 mg in the placebo arm, a reduction of almost 20%. However, cumulative dose is a proxy. It states how much steroid was administered; it does not convey what effect that steroid had on the patient.
The GTI was included as an exploratory endpoint in GCAptAIN, and the GTI-Aggregate Improvement Score (GTI-AIS) tells a markedly different story from the dose data alone.
At week 52, GTI-AIS values were 23.2 for SEC-300 versus 73.1 for placebo. The GTI-Cumulative Worsening Score (GTI-CWS) at week 52 was 53.0 for SEC-300 versus 100.4 for placebo.
These are not marginal differences, with the minimal clinically important difference (MCID) for the GTI being 10 points.[2] This represents a substantive reduction in measurable steroid-toxicity burden in a patient population where toxicity exacerbates pre-existing vulnerability.
This is the third time the GTI has been deployed as an endpoint in GCA. The first was the GiACTA trial,[2] which established baseline steroid-toxicity profiles in GCA patients and underpinned the predictive work published by Patel et al. The second was the TitAIN phase 2 study, in which exploratory GTI data were consistent with reduced steroid-toxicity in the secukinumab arm.[3] GCAptAIN elevates the GTI from an exploratory measure to a pre-specified secondary endpoint, and the signal is consistent and directionally strong.
Subgroup findings and the REPLENISH context
Two subgroup analyses merit attention for clinical development teams working in this space.
In patients with PMR symptoms at baseline, approximately a third of the GCAptAIN population, sustained remission was 34.8% with SEC-300 versus 21.1% with placebo. This is complementary to data from the REPLENISH phase 3 trial (Stone et al., currently under review), which evaluated secukinumab in PMR and is reported to have met its primary and key secondary endpoints, including significant reductions in both cumulative steroid dose and steroid-toxicity.
The clinical and pathophysiological overlap between GCA and PMR is well established. Taken together, GCAptAIN and REPLENISH begin to define a pattern: secukinumab produces a consistent and measurable reduction in steroid-toxicity burden across related IL-17A-driven inflammatory conditions, regardless of whether the remission endpoint is achieved.
The safety profile of secukinumab in GCAptAIN was consistent with more than ten years of real-world data across its approved indications. The lowest frequency of serious adverse events was observed in the SEC-300 arm. Infection rates were lower in both secukinumab arms than in the placebo arm.
Implications for clinical development
The GCAptAIN results underscore a measurement problem central to drug development in steroid-dependent diseases. Dose reduction does not and cannot quantify the healthcare costs of steroid-toxicity. A trial that records a reduced cumulative steroid dose without a direct, validated steroid-toxicity measure cannot characterize the clinical benefit of a steroid-sparing intervention.
As research into shorter steroid tapers in GCA has demonstrated, the relationship between dose, duration, and toxicity is not linear. The GTI provides the instrument to make that relationship legible in a clinical trial setting as a direct measure of health.
GCAptAIN adds an important data point to that body of evidence. The trial did not demonstrate statistical superiority on its primary endpoint. But in quantifying the steroid-toxicity benefit of a shorter taper alongside an active agent, it demonstrates why measuring steroid-toxicity directly represents an advancement in research and practice.
References
- Stone JH, Venhoff N, Buttgereit F, et al. Secukinumab for Giant Cell Arteritis. NEJM Evidence. Published online June 3, 2026. https://doi.org/10.1056/EVIDoa2600112
- Stone JH, Tuckwell K, Dimonaco S, et al. Glucocorticoid toxicity in patients with giant cell arteritis: findings from the GiACTA trial. RMD Open. 2022;8(2):e002550.
- Venhof N et al. Safety and efficacy of secukinumab in patients with giant cell arteritis (TitAIN): a randomized, double-blind, placebo-controlled, phase 2 trial, The Lancet Rheumatology 2023; 5:e341-e350. https://doi.org/10.1016/S2665-9913(23)00101-7