medwireNews: Follow-up results from a phase II trial indicate that patients with systemic lupus erythematosus (SLE) who receive treatment with ustekinumab in addition to standard therapy continue to experience benefits at 48 weeks.
The primary findings from this trial, reported previously by medwireNews, demonstrated that SRI-4 response rates at week 24 were significantly higher among the 60 participants who received add-on ustekinumab compared with the 42 given placebo, at 62.0% versus 33.0%. Glucocorticoids were the most frequently used standard therapy, taken by 85.0% and 80.9% of patients in the ustekinumab and placebo groups, respectively.
Now, Ronald van Vollenhoven (University of Amsterdam, the Netherlands) and co-investigators have shown that the proportion of patients in the ustekinumab group achieving an SRI-4 response was maintained over time, with 63.3% meeting this endpoint at the 48-week follow-up.
SRI-5 and -6 response rates were also sustained among ustekinumab-treated patients at 48 weeks, as were mean changes from baseline in SLEDAI-2K and Physician’s Global Assessment scores.
The researchers explain that ustekinumab was given as a single weight-guided dose administered by intravenous infusion, followed by subcutaneous injections of the interleukin (IL)-12/23 inhibitor at a dose of 90 mg every 8 weeks. Participants in the placebo group crossed over to subcutaneous ustekinumab at week 24.
Among the 33 participants who switched from placebo to ustekinumab, SRI-4 response rates increased from 42.4% at week 24 to 54.5% at week 48, with similar improvements occurring for SRI-5 and -6 response rates.
van Vollenhoven et al say that ustekinumab-treated patients had a low risk for severe flare (≥1 new BILAG A domain score) throughout the study, with rates of 2.1 per 10,000 patient–days from baseline to week 24 and 1.1 per 10,000 patient–days from week 24 to 48. Among placebo-treated patients, the rate of severe flares per 10,000 patient–days was 8.4 from baseline to week 24, decreasing to 4.6 after the switch to ustekinumab.
The investigators report in Arthritis & Rheumatology that there were no new safety findings in the trial, and adverse events “were consistent with the known safety profile of ustekinumab in patients with psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis.”
In all, 81.7% of ustekinumab-treated patients experienced adverse events during an average total follow-up of 41.3 weeks, most commonly infections. The most frequently occurring infections were of the urinary tract (18.3%), followed by upper respiratory tract infections (17.2%) and nasopharyngitis (8.6%).
The study authors caution that their phase II study had a number of limitations, including small patient numbers and no placebo control after week 24.
Moreover, a “steroid-sparing effect of ustekinumab could not be ascertained in this study” because only approximately 9–12% of patients had their glucocorticoid dose reduced despite dose reductions being permitted after week 24, they add.
And the team concludes: “The efficacy and safety of ustekinumab, including the potential for reduction in glucocorticoid dose, are being evaluated further in a broader population of SLE patients in an ongoing phase III program.”
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