In a study of belimumab (Benlysta) for systemic lupus erythematosus (SLE) with the longest duration of follow-up, the efficacy and safety of this monoclonal antibody plus standard-of-care treatment persisted for up to 13 years, a multicenter open-label continuation study found.
Among patients who had responded to treatment during a 52-week double-blind phase II trial and then were enrolled in the continuation study, the number of patients who were responders on the multifaceted endpoint referred to as the SLE Responder Index rose from 32.8% at week 16 in year 1 to 75.6% at week 32 in year 12. This reflected not only persistent and increasing efficacy, but also the expected decline in the number of patients remaining in the study, said Daniel J. Wallace, MD, of the University of California, Los Angeles, and colleagues.
With regard to safety, the overall number of patients reporting any adverse event was 295/100 patient-years during year 1 of follow-up and 199/100 in year 6, while the rate of patients reporting a serious adverse event was 29.8/100 patient-years in year 1 and 32.6/100 in year 6, the researchers reported online in Arthritis & Rheumatology.
“For the large percentage of patients who remained in the study (70.1% at 5 years, 60.1% at 7 years, and 44.3% at 10 years), the results suggest that patients who initially respond to belimumab and continue to receive treatment are likely to experience long-term benefits with continued or improved disease control,” Wallace and colleagues wrote.
Intravenous belimumab (10 mg/kg every 4 weeks) has been licensed for use in SLE since 2011 in the U.S., and is now available in more than 60 countries. Previous analyses of the current study determined that safety and efficacy were maintained through 7 years, and the current analysis is the study’s final report.
The original double-blind phase included 476 patients, and 298 were enrolled in the continuation study, with 96 still in the study at its conclusion. The median duration of exposure was 3,334 days, and the median number of infusions was 115.5.
Most of the patients were women, mean baseline age was 43, and mean disease duration was 9 years. Mean disease activity score at baseline was 8.4, and one third of patients were on corticosteroid dosages above 7.5 mg/day.
The most common reasons for withdrawal were the desire to become pregnant and difficulties in clinic attendance. Withdrawals because of a lack of efficacy were scarce, reaching a maximum of six patients during year 3, the researchers noted.
The percentage of patients who had a four point or greater reduction in their Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) increased from 33.7% at week 16 in year 1 to 76.7% at week 32 in year 12, while the percentage achieving a SELENA-SLEDAI of 2 or lower (low disease activity) rose from 8.4% at baseline to 62.2% at week 48 in year 12.
Rates of disease flares and severe flares were low throughout the study, at 1.1 and 0.1/patient-year, respectively.
Among the 64.5% of patients who were using corticosteroids at baseline, 13.2% were able to discontinue the steroid, and the median change from baseline in daily prednisone dose was 88% by year 13.
The most common adverse events were arthralgias, upper respiratory tract infections, sinusitis, urinary tract infections, and headache, the researchers reported. A total of 14.9% of patients withdrew because of adverse events.
The rate of serious infections was stable, at 3.7/100 patient-years in year 1 and 6.7/100 during year 11. The malignancy rate was 0.6/100 patient-years.
Depression was reported in 9.8/100 patient-years, and six cases of suicide attempt/self harm occurred, with one fatality. Other causes of death (n=7) included cardiac arrest, pneumonia, and respiratory failure. Previous SLE studies have reported higher mortality rates, and the researchers noted that the low death rate in this study may have resulted from the exclusion of patients with central nervous system involvement or active nephritis. The steroid-sparing effects of belimumab and its effects in limiting organ damage also may have contributed, the team observed.
Grade 3 and 4 low neutrophil counts were seen in 15.2% and 2.7% of patients, respectively.
“That approximately one-third of patients continued to receive belimumab for at least 10 years is extraordinary, particularly in light of adherence rates to other medications used for and studied in SLE,” Wallace and co-authors wrote.
They also stated that further important research should focus on the effects of stopping belimumab among patients with stable low disease activity, and noted that a study is already underway to explore this.
Limitations of the study, the researchers said, included its open-label design and variations in standard-of-care treatments.
The study was funded by GlaxoSmithKline and Human Genome Sciences.
The authors reported financial relationships with GlaxoSmithKline, Eli Lilly EMD Serono, Celgene, Aurinia, Genentech, AstraZeneca, Bristol-Myers Squibb, Janssen, Amgen, Sanofi, AbbVie, Immupharma, Servier, InCyte, ILTOO, Glenmark, Astellas, Remegan, Pfizer, Johnson & Johnson, Anthera, Xencor, and Gilead; several authors are employees of GlaxoSmithKline.