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Highlights from

American College of Rheumatology

annual meeting 2018

Chicago, Illinois 19-24 October 2018

Complete renal response reached earlier with abatacept versus placebo in lupus nephritis

Take-home messages
  • The study failed to meet its primary endpoint of complete renal response at 1 year
  • Abatacept-treated patients reached complete renal response earlier than placebo-treated patients, and this was sustained at a higher rate
  • Safety consistent with known profile for abatacept
“Abatacept patients reached complete renal response earlier and sustained their complete renal response at a higher rate [compared with placebo], a benefit driven by improvement in proteinuria.”

Dr Mary Dooley Rheumatologist, University of North Carolina at Chapel Hill, US

Abatacept for 1 year failed to provide complete renal response in patients with active class III or IV lupus nephritis, however it did provide more rapid improvement in proteinuria than placebo, which led to more sustained complete renal response up to 3 years, show data presented at the 2018 American College of Rheumatology/ Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting.

Lead author and presenter was Dr Mary Dooley, from University of North Carolina at Chapel Hill, US. “The study failed to meet its primary endpoint of complete renal response at 1 year, however abatacept patients reached complete renal response earlier and sustained their complete renal response at a higher rate [compared with placebo], a benefit driven by improvement in proteinuria,” she said. “Renal function recovery [eGFR] also occurred earlier in patients on abatacept treatment, and improvements in SLE [systemic lupus erythematosus]-related biomarkers were more pronounced in abatacept patients over 3 years,” she added.

As an immunomodulator that inhibits CD28-mediated T-cell activation, abatacept works by binding to CD-80 and CD-86. The premise upon which this phase III study was initiated was the phase II study, which found that intravenous (IV) abatacept demonstrated biologic activity and was well tolerated in patients with lupus nephritis. The phase III study discussed here assessed the efficacy and safety of IV abatacept versus placebo on background therapy for the treatment of active proliferative lupus nephritis.

The 24-month randomised, multicentre, double-blind study with a blinded long-term extension randomised 405 patients on a 1:1 ratio to placebo or IV abatacept 30 mg/kg for 3 months, followed by abatacept at ~10 mg/kg every 28 days on a background of mycophenolate plus corticosteroids up to 2 years.

The primary endpoint was complete renal response at 1 year that comprised a composite measure requiring maintenance of GFR, urine protein-to-creatinine ratio (UPCR) ≤0.5, absence of urinary cellular casts, and corticosteroids of no more than 10 mg/day. Secondary endpoints included complete renal response for nephrotic patients, as well as change in UPCR in nephrotic patients and the overall population. Blinded data up to 3 years were reported by Dr Dooley.

Patients included in the study had lupus nephritis III or IV, and UPCR ≥1; were aged an average of 33 years; 90% were women; mean UPCR at screening was 3.78, and mean eGFR at screening was 95 mL/min. Overall, 77% on abatacept and 79% on placebo completed year 1, and 48% and 42% respectively entered the ongoing extension from year 3. Fewer patients on abatacept (14%) discontinued in year 2 than on placebo (22%).

Dr Dooley reported that there were no significant differences between treatment arms in the proportion of patients with complete renal response after 52 weeks, with 35.1% on abatacept, and 33.5% on placebo (p=0.73). “Sustained complete renal response (over two successive visits) occurred earlier and more frequently in abatacept-treated patients, and renal response rates were higher and non-response rates were lower in the abatacept arm in year 2 and 3,” she reported.

The adjusted mean change from baseline in UPCR over time showed a difference between placebo and abatacept of -0.27 at day 365, and -0.41 at day 729 in favour of abatacept. The adjusted mean change from baseline in eGFR over time showed no between-group difference over 3 years.

Safety profile findings in year 1 were consistent with the known profile of abatacept with a serious adverse event rate of 24% on abatacept, and 19% on placebo. This event rate improved after year 1 with 6% on abatacept and 13% on placebo. The incidence of death over 3 years was 7 in each group.

Serious infections were 29 versus 20 in abatacept versus placebo in year 1, and 7 versus 9, respectively, in year 2. There were more patients with severe pneumonia in patients on abatacept versus placebo at 14 versus 6 in year 1, and 3 versus 1 in year 2. Severe herpes zoster also had a higher incidence in patients on abatacept at 5 versus 3 in year 1. Very few opportunistic infections were observed at 6 versus 4 in abatacept versus placebo, and patients with osteonecrosis during the study were 2 on abatacept and 10 on placebo.

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The content and interpretation of these conference highlights are the views and comments of the speakers/authors.

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