Telitacicept tied to higher SRI-4 response in SLE patients

Among patients with active systemic lupus erythematosus (SLE), treatment with telitacicept significantly increased SLE Responder Index 4 (SRI-4) response rate at week 52 compared with placebo, according to a study presented at EULAR 2023.

SRI-4 response is a composite endpoint used in SLE clinical trials to assess disease activity and response to treatment, such as reduction in disease activity in the preceding 10 days, resolution of skin rashes, flare rate, and reduction in daily oral corticosteroid dosage. [https://www.multivu.com/players/English/8648251-remegen-clinical-trial-systemic-lupus-erythematosus-sle/]

This phase III trial met its primary endpoint, with a significantly higher proportion of patients achieving an SRI-4 response at week 52 with telitacicept compared with placebo, said Prof Ronald van Vollenhoven from Amsterdam University Medical Center, Amsterdam, the Netherlands, who presented the study.

At week 52, 67.1 percent of the patients who received telitacicept had an SRI-4 response, while only 32.7 percent of those treated with placebo achieved this outcome (p<0.001). [EULAR 2023, abstract OP0137]

Of note, the between-group difference was evident as early as week 4, continued to increase, and then stabilized around 16–20 weeks of treatment, Vollenhoven noted.

“Telitacicept (TACI*-Fc fusion protein) is a novel BLyS (B-lymphocyte stimulator)/APRIL (a proliferation-inducing ligand) dual inhibitor, which has been approved in 2021 in China for the treatment of patients with active SLE,” said Vollenhoven.

This phase III, double-blind, placebo-controlled trial analysed 335 patients (mean age 35 years) with active SLE who had a baseline SELENA-SLEDAI** mean score of 11.5, indicating a high-disease activity. Participants were randomized to receive either once-weekly subcutaneous telitacicept 160 mg (N=167) or placebo (N=168) for 52 weeks in addition to standard therapy.

With regard to secondary endpoints, time to first SLE flare was reduced among patients treated with telitacicept compared with placebo (115 vs 198 days; p<0.001).

Telitacicept recipients also achieved significant reductions in immunological biomarkers, including IgG, IGA, and IgM levels, as well as CD19+ B cells, from baseline to week 52 compared with placebo recipients (p<0.001 for all).

Rapid and sustained improvements in C3 and C4 levels were also observed with telitacicept compared with placebo at week 52 (p<0.05 and p<0.001, respectively).

In terms of safety, the incidence of treatment-emergent adverse events (TEAEs) was 91.6 percent with telitacicept and 83.5 percent with placebo.

“Many AEs did occur, and I would like to remind those of you who are not so familiar with clinical trials that anything that occurs during a trial can be considered as an AE without attribution to the study drug,” Vollenhoven mentioned.

However, the placebo group experienced more serious AEs (14.3 percent vs 7.2 percent) and serious infections (5.4 percent vs 1.2 percent) than the telitacicept group.

No deaths were reported in either of the treatment group.

“Overall, telitacicept treatment achieved significantly higher SRI-4 response rates than placebo … It also lowered the risk of SLE flares, particularly severe flares, and did not increase the risk of infections,” said Vollenhoven.

“Telitacicept also showed good clinical benefits and a favourable safety profile in patients with moderate-to-severe SLE,” Vollenhoven noted.

As telitacicept is also used in other parts of the world, a global REMESLE-1 phase III trial is currently enrolling, he added.