The trial’s primary end point was the proportion of patients who achieved SRI-4 (SLE Responder Index 4) at week 32. This is defined as an improvement of SLEDAI of 4 points or more, along with a physician’s global assessment score that has not worsened by 10% or more, with no new severe symptoms and no more than one new moderate symptom as assessed by BILAG.13
Many lupus trials have higher rates of placebo response compared to trials in other disease states, such as rheumatoid arthritis, and the same was true here.14 For the SRI-4 end point, the response rate was 34% in patients on placebo. However, the trial still met its primary end point, with 58%, 50% and 45% of patients taking deucravacitinib (i.e., 3 mg daily, 6 mg twice daily and 12 mg daily, respectively) achieving SRI-4 at week 32, although this just missed statistical significance in the 12 mg daily group.
“There was no added effect in efficacy by increasing the dose,” Dr. Pike said. She speculated this may be because of additional effects on other parts of the immune system stimulated at higher doses; ongoing studies of cytokine response may help elucidate that.
This trend of better efficacy in those patients receiving the lowest dose of deucravacitinib was repeated across all secondary end points. For example, the BICLA (BILAG-based composite assessment), is another overall response end point comparable to the SRI-4. Dr. Pike pointed out that at week 48, “The BICLA and SRI-4 both showed very similar response rates and dose effects as the primary end point.” These responses were statistically significant in the 3 mg twice daily group, with clinically meaningful differences not reaching statistical significance in the other groups.
Dr. Pike noted that this trend continued for the Lupus Low Activity Disease State (LLDAS), the Cutaneous Lupus Erythematosus Disease Area and Severity Index-50 (CLASI-50) and active joint count assessments. “You saw rather robust treatment effects at the 3 mg BID doses,” added Dr. Pike.
Importantly, safety data showed no increase in adverse events or serious adverse events in the treatment group, with no cardiac or thromboembolic events and no increased risk of COVID-19 or herpes zoster. Rates of skin-related events such as rash and acne were higher in the deucravacitinib groups, most pronounced at higher doses. Blood testing showed that liver and renal function were not affected, nor were red or white blood cells. “The safety was very similar with what has been seen in psoriasis and psoriatic arthritis trials,” said Dr. Pike.
