Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seems to benefit rituximab (Rituxan), according to data from the Register of Biologists of the Lupus Assessment Group of the British Isles (BILAG-BR).
In fact, the percentage of patients with active disease, according to the BILAG-2004 or SLEDAI-2K index (SLE Disease Activity Index 2000), decreased significantly (Pg <.0001) when comparing pre- and post-rituximab treatment scores. The dose of oral steroids used was also reduced.
Interestingly, the use of concomitant cyclophosphamide could improve the level of improvement observed in some patients, Trixy David, MBBS, reported during an abstract session at the annual conference of the British Society for Rheumatology.
“Large-scale studies are warranted to establish the efficacy of rituximab alone or in combination with cyclophosphamide in the treatment of neuropsychiatric lupus,” said David, a clinical researcher at the University of Manchester (England) and registrar specializing in rheumatology at the Foundation. of the National Health Service at the University of Manchester.
Neil Basu, MBChB, Ph.D., who chaired the virtual session, described the findings as “clarifying” and “descriptive.”
The study “provides some interesting data, which should be verified in a robust, randomized clinical trial,” he agreed, not that doctors should now start using rituximab for their NPSLE cases.
Basu, who is a senior clinical professor of rheumatology and an honorary consultant in rheumatology at the Institute of Infection, Immunity and Inflammation at the University of Glasgow, added: “It is really important that we do these studies to help substantiate this trial. they are obviously very expensive and require solid evidence before following this trail. I think that data has been really very enlightening in that regard. “
Rationale for Rituximab in Neuropsychiatric Lupus
Management of patients with NPSLE remains an area of substantial unmet needs. According to one recent review in Rheumatology, “there is a shortage of controlled clinical trials to guide management” and “therapeutic options include symptomatic, antithrombotic, and immunosuppressive agents that are supported by observational cohort studies.”
Despite being observed in at least half of all patients with SLE, neuropsychiatric disease “is not well studied in patients with lupus, as many large-scale trials tend to exclude patients with active neurological disease,” David said. .
Although it is unclear why a neuropsychiatric disease occurs in SLE, it could be “as a result of a vascular injury or an interruption of the blood-brain barrier, thus allowing the passive diffusion of autoantibodies and cytokines through the spinal fluid. brain, thus generating a proinflammatory response, “David suggested.
“We know that B cells are involved in the pathogenesis of lupus and rituximab is a chimeric monoclonal antibody that selectively targets CD20-positive B cells and mediates B cell depletion.” It should be noted that there are some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the UK.
About BILAG-BR and the results
“Our aim was to describe the baseline characteristics and short-term efficacy of rituximab in patients treated with neuropsychiatric lupus at BILAG-BR,” David explained.
Started in 2009, the ANNEX-BR it now contains information on more than 1,400 people with SLE who have been recruited at 62 centers in the UK. Its purpose is to evaluate the long-term safety and efficacy of biologic drugs versus standard immunosuppressive therapy, such as azathioprine, mycophenolate mofetil, cyclophosphamide i cyclosporine. To date, 1,229 patients have been treated with biological products, of which 1,056 have received rituximab.
A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making it “the largest prospective observational cohort to date, to our knowledge,” David said.
The mean age of the patients was 45.5 years, most were women (82%) and white (74%). The mean duration of the disease was 11.5 years.
A total of 96% had multiple organ involvement and not just neuropsychiatric disease, and 91% were positive for antineutrophil antibodies.
The six main neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affect 27.5% of patients); acute confessional status or mononeuropathy (each observed in 10% of patients); i convulsive disorder and polyneuropathy, observed in 8.6% and 8.7%, respectively, of patients. These results are in line with one Meta-analysis of 2011, David pointed out.
BILAG-2004 scores before and after rituximab treatment were available for 50 patients. The number of patients with a BILAG A score dropped from the initial 24 (48%) to 7 (14%) after rituximab treatment and the number with a BILAG B score decreased from the initial 26 (52%) to 4 (8). %) after rituximab (both Pg <.0001).
There was also a reduction after rituximab treatment in the percentage of patients classified as primarily with central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both. (11% vs. 8%).
Total SLEDAI-2K scores also decreased after rituximab treatment, from a median of 12 at baseline to 2 (Pg <.0001).
Oral pre and post-rituximab prednisolone the doses were an average of 15 mg and 10 mg (Pg = .009).
“Our data come from a real-world environment of patients who had active neuropsychiatric disease and were treated with rituximab,” David said. Of course, there are many limitations that go hand in hand with observational studies.
“There was the problem of lack of data,” David said. It was difficult or not possible to determine what doses of steroids patients took after rituximab therapy, especially in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around time at which patients started or stopped rituximab treatment.
“These could have acted as possible confounders,” he acknowledged.
Basu noted, “My main nebulosity is the uncertainty of why these patients improved. Yes, they had rituximab, but I’m also sure they probably received high doses of steroids if they were quite severe.” Lupus of the CNS which was classified as BILAG-A or B. “
It can also be administered to patients methylprednisolone when clinicians are really concerned, he continued, and “as was clearly pointed out,” quite a bit of information was missing from a steroid perspective.
David and co-investigators reported that they had no conflicts of interest. BILAG-BR is funded by Lupus UK, GlaxoSmithKline and Roche. Basu did not claim to have disclosures.
This article originally appeared on MDedge.com, which is part of the Medscape professional network.