By Lucy Piper, medwireNews Reporter
medwireNews: Telitacicept used in addition to standard therapy shows promising efficacy in Chinese patients with active systemic lupus erythematosus (SLE), suggests a phase 2b trial published in the Annals of the Rheumatic Diseases.
“These results support further investigations of telitacicept in clinical trials involving more diverse populations and larger samples sizes”, say Fengchun Zhang (Peking Union Medical College Hospital, Beijing, China) and colleagues.
Telitacicept is a fusion protein that inhibits both B lymphocyte stimulator and proliferation-inducing ligand, which the researchers say has “the potential to provide more complete inhibition of autoantibody production.”
For the study, conducted at 29 hospitals in China, 249 patients with active autoantibody-positive SLE disease, defined as an SLE Disease Activity Index (SLEDAI) score of at least 8 points, with at least 6 points from clinical symptoms, were randomly assigned to receive weekly subcutaneous telitacicept at one of three doses – 80 mg (n=62), 160 mg (n=63), 240 mg (n=62) – or placebo (n=62) in addition to their standard treatment.
The mean age of the patients was 33.9 years, the majority (94.4%) were women and all were of Asian ethnicity. The mean disease duration was 7.14 years. Allowed concomitant treatment included nonsteroidal anti-inflammatory drugs, glucocorticoids (≤60 mg/day prednisone or equivalent), antimalarials and immunomodulators.
Glucocorticoid doses could be increased during the first 24 weeks but by no more than 25% or 5 mg above the baseline dose, and tapering was recommended if SLE activity improved for at least 4 weeks. Changes to immunosuppressants and antimalarials were only allowed in the first 16 weeks.
The researchers report that despite “high response rates in the placebo group” that were likely due to “the permitted use of prednisone and other medications, along with a high rate of concomitant antimalarial medication,” receipt of telitacicept at all doses was associated with a significantly higher SLE Responder Index (SRI)-4 rate at 48 weeks.
The highest rate was seen among patients receiving the 240 mg dose, at 75.8%, followed by 71.0% among those receiving 80 mg and 68.3% among those receiving 160 mg. The rate among patients in the placebo group was 33.9%, with a significant difference seen between controls and the patients receiving telitacicept 240 mg from as early as week 4.
Significant treatment differences at all doses were also seen for secondary endpoints. The proportion of patients achieving at least a 4-point reduction in SLEDAI score from baseline ranged from 75.8 to 79.0% with telitacicept versus 50.0% with placebo, and for most patients treated with telitacicept (92.1–96.8%) there was no deterioration in score on the Physician’s Global Assessment, compared with 75.8% of patients treated with placebo.
Zhang et al note that “[r]educing steroid dose is an important goal of SLE treatment,” and their findings suggest that telitacicept treatment may enable this. They found that, at week 48, 40.7% of patients receiving telitacicept 240 mg reduced their prednisone dose to below 7.5 mg/day or by at least 25% from baseline, compared with 21.3% of those receiving placebo, a significant difference.
Telitacicept was also well tolerated with similar rates of adverse events (AEs) to that with placebo, at 90.3–93.5% versus 82.3%, most of which were mild to moderate in severity. Serious AEs occurred in 12.9–15.9% of telitacicept-treated patients compared with 16.1% of those given placebo, again with no significant difference between the groups.
Infections were more common in the telitacicept groups, occurring in 72.7% of patients across the three groups combined versus 64.5% of those in the placebo group. The most frequent of these were upper respiratory tract infections, urinary tract infections and shingles.
There was one death among patients in the telitacicept 240 mg group, due to aggravation of SLE, infection-induced pancytopenia and coagulopathy.
The researchers conclude that “[d]espite the approval of biological therapies such as belimumab and anifrolumab for patients with active SLE, there is still an unmet medical need for therapies with more satisfactory efficacy and safety profiles”, and that “[t]elitacicept provides a novel option”.
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Ann Rheum Dis 2023; doi:10.1136/ard-2023-224854