LONDON — Adding belimumab (Benlysta) to standard treatments for systemic lupus erythematosus was associated with significantly lower rates of disease flares, a claims-based analysis revealed.
In an “as treated” analysis, there was an approximately 30% decrease in the incidence rate of moderate-to-severe flares during the 12 months after the initiation of belimumab therapy, according to Karen Costenbader, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital in Boston.
“High flare rates in lupus have been shown to be associated with organ damage, resource use, and cost, and this is the first long-term, real-world evidence of clinical outcomes after belimumab initiation,” she said at the annual European Congress of Rheumatology annual meeting.
Belimumab is a human monoclonal antibody that binds to and inhibits B-lymphocyte stimulator (BLyS). It was approved in 2011 for the treatment of patients with active, autoantibody-positive lupus as an add-on to standard therapy.
The clinical efficacy of belimumab was demonstrated in two large phase III studies, the BLISS trials. “However, the effectiveness of belimumab in a real-world setting still needs to be evaluated,” she said.
Costenbader’s group analyzed flare incidence rates among patients diagnosed with lupus and included in the U.S. Truven Health MarketScan commercial database from 2010 to 2014.
The index date was the first infusion of belimumab, and the 6 months before the index date was considered the baseline period.
Moderate flares were those episodes requiring initiation of an oral steroid with prednisone-equivalent doses between 7.5 mg/day and 40 mg/day, the initiation of immunosuppressive therapy other than cyclophosphamide, or a claim for an emergency department (ED) visit with a primary diagnosis of lupus or a lupus-related condition.
Severe flares were defined as initiation of oral steroids in prednisone-equivalent doses greater than 40 mg/day, the initiation of cyclophosphamide, or inpatient admission with a primary diagnosis of lupus or a lupus-related condition.
The duration of each flare episode was set to 30 days by algorithm default.
A total of 1,835 patients were included in the analysis, of whom 94% were women with a mean age of 43.
Lupus manifestations at baseline included arthritis in 46%, arthralgias in 43%, mood disorders in 34%, rash in 27%, anemia in 20%, and lupus nephritis in 7%. Other comorbidities reported in the 6-month baseline period before the index date included infections, hypertension, pulmonary disease, and osteoporosis. During the baseline period, 27% had ED visits and 15% had inpatient admissions.
Patients had moderate-to-severe disease activity and were on a variety of medications at baseline, including oral steroids in 70%, antimalarials in 70%, immunosuppressants in 60%, and nonsteroidal anti-inflammatory drugs in 32%.
In the 6-month baseline period before the initiation of belimumab, the incidence rate per person-year was about three.
In an as-treated analysis, which included person-time spanning the duration of drug exposure to 1 month after the last infusion, the incidence rate fell below three and was sustained at that level beyond 36 months. However, in that analysis, only 52 patients were still included at 3 years.
In an intent-to-treat analysis, which included all person-time follow-up, the incidence rate of flares fell below three per person-year after the initiation of belimumab, and was sustained at 2.5 at 36 months, with 191 patients still being included.
The decrease was highly statistically significant in both analyses (P<0.001), she reported.
“The initiation of belimumab was associated with a sustained decrease in moderate-to-severe flares compared with the period prior to initiation, and we saw consistent results both in the as-treated and intent-to-treat populations, she said.
“These results reinforce the findings from the belimumab BLISS randomized trials. We did see some indication of higher lupus flare rates than observed in other cohort studies at academic sites and in claims database studies. However, this is to be expected in a patient population initiating belimumab, who are likely to have more severe lupus and a higher likelihood of flaring,” Costenbader said.
A limitation of this preliminary work was the measurement of flare severity based on an algorithm that uses claims-based proxies such as the use of medications and hospitalizations, so miscoding may have occurred. In addition, the analyses were not controlled for oral steroid and other medication use.
She and her colleagues plan additional analyses, looking at discontinuation patterns and reasons for treatment withdrawal, as well as a comparative effectiveness study of belimumab initiators versus immunosuppressive initiators.