Large-scale phase 3 clinical trials have already demonstrated the clinical efficacy of belimumab (Benlysta) in patients with systemic lupus erythematosus (SLE), which served as the basis for the US Food and Drug Administration approval of this medication for adult patients with active, autoantibody-positive SLE who are receiving standard therapy. New data from postmarketing analyses of belimumab therapy in clinical practice settings have been presented at the 2013 annual meeting of the American College of Rheumatology held in San Diego, California from October 25-30.
Collins and colleagues (Abstract 1740) examined the clinical outcomes associated with 12 months of belimumab treatment in clinical practice settings in the United States. Their study, known as the OBSErve study, was a multicenter retrospective chart review from community-based rheumatology practices that treated more than 10 patients with SLE annually. Data from 384 patients with SLE who had received ≥8 infusions of belimumab 10 mg/kg were collected for the 6 months before the initiation of belimumab therapy, the first 6 months after the initiation of belimumab, and the period from 6 to 12 months after the initiation of belimumab. The primary outcome measure was physician impression of change in overall SLE disease, as well as in specific disease manifestations. The patients’ mean age in this cohort was 42 years, 52% were Caucasian, 26% were African American, and 90% were female. Approximately 98% of the patients in the study were determined to have moderate or severe SLE, based on the physicians’ clinical judgment.
During months 0 to 6 of belimumab therapy, a ≥20% improvement in SLE disease activity was observed in 88% of the patients, ≥50% improvement in 47%, and ≥80% improvement in 11%. During months 6 to 12 of belimumab therapy, a ≥20% improvement in SLE disease activity was observed in 71% of the patients, ≥50% improvement in 30%, and ≥80% improvement in 11%. Of the 384 patients analyzed at month 12 who had received concomitant steroids at baseline, 104 (35%) were able to completely discontinue the use of corticosteroids at 12 months, and mean corticosteroid use among those who continued using steroid therapy decreased from a mean of 19.4 mg daily at baseline to 8.4 mgdaily at month 12. For the 96 patients who had Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores available, a 59% reduction was seen in these scores from baseline to 12 months. In addition, from baseline to 12 months, the mean Physician’s Global Assessment and Patient’s Global Assessment scale scores improved by 54% (N = 100) and 56% (N = 78), respectively, over this time. The number of objective clinical manifestations per patient also declined over the first 6 month of the OBSErve study, with a 21% reductionin rash, a 17% decrease in high anti-dsDNA antibody levels, and a 19% decrease in patients with low complement levels.
These data show that in clinical practice, patients with moderate to severe SLE demonstrate continued improvement in clinical outcomes and a significant reduction in steroid use over 12 months of treatment with belimumab. Just as striking, the OBSErve study showed that healthcare resource utilization by patients receiving belimumab decreased significantly over the 12 months of the trial, including significant reductionsin unscheduled office visits, emergency department visits, and ancillary care service use.
In a similar presentation by Yazdany and colleagues (Abstract 1605), the postmarketing experience with belimumab in routine clinical practice was assessed among 15 centers in the United States that were participating in the Lupus Clinical Trials Consortium national patient registry. Among 1189 patients in the registry who were followed for a mean of 23.2 months, 68 patients (5.7%) started receiving belimumab. The mean age of these patients was 39 years, 94% were female, 41% were Caucasian, 47% were black, and the mean disease duration was 10.7 years. The patients were treated with concomitant glucocorticoids (82%), azathioprine (27%), mycophenolate mofetil (31%), methotrexate (15%), and/or an antimalarial (75%).
The most common reasons for starting belimumab therapy included the corticosteroid-sparing effects of belimumab or the need to treat a lupus-related disease manifestation, such as arthritis, mucocutaneous disease, or serositis. At 6-month and 12-month follow-up, the mean SELENA-SLEDAI scores improved significantly by 32% and 52%, respectively (P <.05); the mean Physician’s Global Assessment scores improved significantly by 33% and 42% at the 6- and 12-month intervals (P <.01). The percentage of positive anti–ds-DNA decreased by 27% at 6 months and by 57% at 12 months. No significant steroid-sparing effect was observed with belimumab therapy. Over the follow-up period, 14 patients discontinued belimumab—4 because of adverse events or intolerability, 3 for lack of efficacy, 3 because they no longer needed it, and 4 as a result of non–disease-related reasons.
These clinical setting results indicate that the postmarketing experience in routine clinical practice for patients with SLE mirrors the results that had been observed with this agent in phase 3 clinical trials.