IL-17A inhibition demonstrates potential for giant cell arteritis
medwireNews: Findings from the phase 2 TitAIN trial support further investigation of the interleukin (IL)-17A inhibitor secukinumab for the treatment of giant cell arteritis (GCA).
Outlining the rationale for the study at the ACR Convergence 2021 virtual meeting, Jens Thiel (University of Freiburg, Germany) said that secukinumab “has shown significant improvements in the signs and symptoms of IL-17A-driven medical conditions,” including psoriasis and psoriatic arthritis, and “has a very favorable long-term safety profile.”
He added that “preclinical data point towards a role of IL-17A in the pathogenesis of giant cell arteritis, and therefore IL-17A inhibition via blocking vascular inflammation is potentially a new therapeutic target” for the condition.
To test this hypothesis, the TitAIN investigators randomly assigned 52 patients aged at least 50 years with new-onset (81%) or relapsing (19%) GCA and no prior biologic exposure to receive 48 weeks of treatment with secukinumab 300 mg every 4 weeks (following a once-weekly loading dose for the first 5 weeks) or placebo. Both treatments were given alongside a 26-week prednisolone tapering regimen, with the dose decreasing from 25–60 mg at baseline to 0 mg at the end of the taper period.
At week 28, 70.1% of the 27 secukinumab-treated patients remaining in the study were in sustained remission, defined as the absence of flare with adherence to the prednisolone taper regimen, compared with 20.3% of the 25 placebo-treated patients, a significant difference.
Thiel noted that flare was defined as recurrence of GCA signs or symptoms after remission, erythrocyte sedimentation rate of at least 30 mm/h, and/or C-reactive protein levels of at least 10 mg/L attributable to GCA.
Participants who were not in remission at week 12, experienced a flare, or could not adhere to the tapering regimen were switched to escape therapy with prednisolone (with dosing based on their clinician’s judgement) and continued to receive the study drug.
At the 52-week follow-up, 59.3% of patients in the secukinumab arm and 8.0% of those given placebo remained in sustained remission. Kaplan-Meier analysis demonstrated that the median time to flare was not reached with secukinumab versus 197 days with placebo.
The presenter said that the total cumulative administered prednisolone dose at 52 weeks was lower in the secukinumab than the placebo group, at an average of 2841 versus 3376 mg.
He reported that secukinumab was “well tolerated” in the TitAIN study, with “no new or unexpected safety signals identified.” The most frequently reported adverse events in the secukinumab arm were hypertension (22.2 vs 32.0% in the placebo group) and nasopharyngitis (18.5 vs 20.0%).
“This proof-of concept phase 2 study supports the further development of secukinumab as a potential treatment for patients with GCA,” concluded Thiel.
And he announced that a phase 3 study of secukinumab for GCA is now underway.
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