Rituximab Benefits Seen in
Neuropsychiatric Lupus

Sara Freeman

April 29, 2021

Patients with neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) seem to benefit from rituximab (Rituxan) therapy, according to data from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR).

Indeed, the percentage of patients with active disease, as scored by the BILAG-2004 index or SLEDAI-2K (SLE Disease Activity Index 2000), fell significantly (P < .0001) when comparing pre- and post-rituximab treatment scores. There was also a reduction in the dose of oral steroids used.

Interestingly, the use of concomitant cyclophosphamide might enhance the level of improvement seen in some patients, Trixy David, MBBS, reported during an abstract session at the British Society for Rheumatology annual conference.

"Larger-scale studies are warranted to establish the effectiveness of rituximab alone, or in combination with cyclophosphamide, in the treatment neuropsychiatric lupus," said David, a clinical research fellow at the University of Manchester (England) and specialist registrar in rheumatology at the Manchester University National Health Service Foundation Trust.

Neil Basu, MBChB, PhD, who chaired the virtual session, called the findings "enlightening" and "descriptive."

The study "provides some interesting data, which should be tested in a robust, randomized clinical trial," he agreed, and not that clinicians should now start using rituximab for their NPSLE cases.

Basu, who is a clinical senior lecturer in rheumatology and honorary consultant rheumatologist 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 support a rationale for such a trial, which are obviously very expensive and require strong evidence before we go down that track. I think these data have really been quite enlightening in that respect."

Rationale for Rituximab in Neuropsychiatric Lupus

Managing patients with NPSLE remains an area of substantial unmet need. According to a recent review in Rheumatology, "there is a dearth 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 seen in at least half of all patients with SLE, neuropsychiatric disease "is not very well studied in patients with lupus, as a lot of large-scale trials tend to exclude patients with active neurological disease," David said.

Although it is unclear why neuropsychiatric disease occurs in SLE, it could be "as a result of vascular injury or disruption of the blood brain barrier, thereby allowing the passive diffusion of autoantibodies and cytokines across through the cerebral spinal fluid, thereby generating a proinflammatory response," David suggested.

"We know 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 transient B-cell depletion," she said. Notably, there have been some small studies suggesting that rituximab may be effective in neuropsychiatric lupus, and it is currently widely used to treat refractory lupus in the United Kingdom.

About the BILAG-BR and Results

"Our aim was to describe the baseline characteristics and short-term effectiveness of rituximab in patients treated for neuropsychiatric lupus within the BILAG-BR," David explained.

Started in 2009, the BILAG-BR now contains information on more than 1,400 individuals with SLE who have been recruited at 62 centers in the United Kingdom. Its purpose is to evaluate the long-term safety and effectiveness of biologic drugs versus standard immunosuppressive therapy such as azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine. To date, 1,229 patients have been treated with biologics, of whom 1,056 have received rituximab.

A total of 74 rituximab-treated patients were identified as having active neuropsychiatric disease, making this "the largest prospective observational cohort to date, to our knowledge," David said.

The median age of patients was 45.5 years, the majority was female (82%) and White (74%). The median disease duration 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 top six neuropsychiatric manifestations were cognitive dysfunction and lupus headache (both affecting 27.5% of patients); acute confessional state or mononeuropathy (each seen in 10% of patients); and seizure disorder and polyneuropathy, seen in a respective 8.6% and 8.7% of patients. These findings are in line with a 2011 meta-analysis, 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 24 (48%) at baseline to 7 (14%) after treatment with rituximab, and the number with a BILAG B score declined from 26 (52%) at baseline to 4 (8%) after rituximab (both P < .0001).

There was also a reduction following rituximab treatment in the percentage of patients categorized as having mainly central nervous system disease (70% vs. 11%), peripheral nervous system disease (19% vs. 6%), or both (11% vs. 8%).

Total SLEDAI-2K scores were also reduced following rituximab treatment, from a median of 12 at baseline to 2 (P < .0001).

Pre- and post-rituximab oral prednisolone doses were a median of 15 mg and 10 mg (P = .009).

Limitations

"Our data are from a real-world setting of patients who had active neuropsychiatric disease and were treated with rituximab," David said. There are of course many limitations that go hand in hand with observational studies.

"There was the issue of missing data," David said. It was difficult or not possible to determine what doses of steroids patients were taking after rituximab therapy, particularly in terms of intravenous steroids, and what doses of any other concomitant disease-modifying therapy might have been around the time that patients initiated or stopped rituximab treatment.

"These could have acted as potential confounders," she acknowledged.

Basu noted: "My major haziness from it is the uncertainty of knowing why these patients improved. Yes, they had rituximab, but I'm sure also that they probably received high doses of steroids if they had quite severe CNS lupus which was categorized as a BILAG-A or a B."

Patients may also be given methylprednisolone when clinicians are really concerned, he continued, and "as was quite clearly pointed out," there was quite a lot of missing data from a steroid perspective.

David and coinvestigators reported having no conflicts of interest. The BILAG-BR is supported by funding from Lupus UK, GlaxoSmithKline, and Roche. Basu did not state having any disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....