The T cell-inhibiting antibody abatacept (Orencia) may help patients with refractory systemic lupus erythematosus (SLE), especially those with articular involvement, according to a small retrospective study.
In the first assessment of the drug for refractory SLE in routine clinical practice, more than half of patients using abatacept for 6 months reduced their SLE Disease Activity Index (SLEDAI) by at least 4 points, and 70% improved according to physician assessment. The treatment was well tolerated overall, according to Raphaele Seror, MD, of Hopitaux universitaires Paris-Sud, Le Kremlin Bicetre in France, and associates.
"These data support conducting new controlled trials of abatacept in SLE patients," the researchers wrote online in Lupus.
Seror and co-authors noted that even with the approval of belimumab (Benlysta), the anti-B lymphocyte stimulator, therapeutic SLE options, and in particular biologics, remain limited.
The study included 11 SLE patients drawn from a French rheumatology network and treated with abatacept for active refractory disease. The primary endpoint was the change in SLEDAI score at 6 months, with response defined as a SLEDAI decrease of 4 or more points. Ten (91%) patients were women, the median age was 44 years, and the median disease duration was 12.5 years.
The indications for abatacept therapy were articular involvement in eight patients, renal or cutaneous involvement in one patient each, and autoimmune thrombocytopenia in one patient. Treatment lasted for a median duration of 7 months. Ten of the patients were positive for anti-double stranded DNA antibodies, and 10 were taking concomitant oral steroids. Seven had had previous biologic exposure.
Five discontinuations at a median treatment duration of 6 months included two for a lack of efficacy (one each primary failure and lupus flare), two for adverse events, and one for intention to conceive.
The median SLEDAI decreased from a baseline score of 6 to 4 (P=0.031), while the median prednisone dose fell only slightly, from 10 mg/day to 9.5 mg/day (P=0.25), but increased in four patients.
The median Disease Activity Score in 28 joints dropped in the eight articular patients from 5.7 to 3.9 (P=0.039), decreasing in seven out of eight cases, and 38% had a complete remission.
Among five patients with cutaneous involvement, three experienced complete remission on abatacept, and one had a partial response. A patient with stage IV lupus nephritis experienced a complete response with no other treatment.
Four adverse events occurred in three patients, but none were severe infections. In the six evaluable participants with elevated anti-DNA antibody levels at baseline, serum levels decreased in four and returned to the normal range in one.
This suggestion of promise provides a counterpart to the somewhat disappointing results from previous trials of abatacept in lupus nephritis. Seror and associates called for further evaluation of abatacept specifically in SLE subgroups with articular and cutaneous manifestations.
The researchers pointed out that changing the response criteria might transform negative results into positive ones since in non-renal lupus, the British Isles Lupus Activity Group response is frequently too stringent a standard to show efficacy. Among suggested new definitions of response is the SLE Responder Index (SRI), which showed belimumab to be effective in two phase III trials.
The SRI includes an efficacy endpoint based on a 4-point SLEDAI improvement, which in the current study showed abatacept to be effective in 50%.
"The authors' findings correlate with some of the findings – especially the response of lupus arthritis – of a previous abatacept clinical trial that, unfortunately, did not meet its primary endpoint," said Petros Efthimiou, MD, of Weill Cornell Medical College in New York, who was not involved in the study.
Interestingly, some of abatacept's effect may be due to cross-talk between T and B cells in SLE, Efthimiou told MedPage Today.
A new randomized placebo-controlled trial of abatacept in polyarticular SLE is under way and incorporates some of the newer clinical endpoints and response criteria. "Hopefully, this ongoing trial will shed some light on efficacy for lupus rash," Efthimiou said.
Among the study's limitations were its retrospective design, its small sample size, and the preponderance of patients with articular SLE.
The authors reported financial relationships with Sanofi, Merck Sharp & Dohme, AbbVie, Bristol-Myers Squibb, Actelion, Pfizer, UCB, Biogen, Roche, Novartis, and GlaxoSmithKline.
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