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Although patients with lupus nephritis recently gained two new add-on treatment options in voclosporin (Lupkynis) and belimumab (Benlysta), there have been little data published with real-world experience in using these drugs.
Voclosporin, a calcineurin inhibitor, was approved by the Food and Drug Administration in January 2021 to treat lupus nephritis in combination with immunosuppressive medication. Belimumab, a human monoclonal antibody and B-lymphocyte stimulator, was approved in December 2020 in the United States as an add-on treatment for lupus nephritis in adults and later in July 2022 for children who are already receiving standard therapy.
How the two drugs are prescribed for patients with lupus nephritis so far appears to be influenced by presence of extrarenal manifestations of lupus, cytotec en farmacias cruz verde proteinuria level, clinicians’ prior experience with belimumab, costs of the drugs, and patient preference, experts said.
Voclosporin’s approval was based on data from the phase 3 AURORA 1 trial and phase 2 AURA-LV trial. AURORA 1 evaluated 357 patients with systemic lupus erythematosus (SLE) and lupus nephritis who were randomized to receive voclosporin or placebo with mycophenolate mofetil and tapered low-dose oral steroids. In the voclosporin group, the results showed a significantly higher complete renal response at 52 weeks, compared with the placebo group, while having a similar adverse event profile. The AURA-LV trial, evaluating efficacy and safety of 179 patients with lupus nephritis, showed adding low-dose voclosporin to induction therapy improved renal response, compared with placebo. AURORA 2, a continuation of the AURORA trial, showed patients with lupus nephritis receiving voclosporin have a stable estimated glomerular filtration rate and reductions in proteinuria up to 3 years of follow-up.
Results from the phase 3 BLISS-LN trial of 448 patients with confirmed lupus nephritis were the basis for belimumab’s approval and showed a significantly higher proportion of patients who received belimumab had a primary efficacy renal response, complete renal response, and significantly lower risk of a renal-related adverse event or death, compared with the placebo group.
Lack of real-world data
The lack of real-world data on either of these treatments can be attributed to lupus nephritis being a rare disease, and the approvals happening fairly recently, experts said.
Dr. Amit Saxena
“This is really due to the recency of the approvals for both of these medications for lupus nephritis,” Amit Saxena, MD, a rheumatologist and assistant professor of medicine in the division of rheumatology at NYU Langone Health in New York, said in an interview.
“It’s too soon for any appreciable data to be collected.”
Dr. Ashira Blazer
Ashira D. Blazer, MD, MSCI, a rheumatologist at Hospital for Special Surgery and assistant professor of medicine at Weill Cornell Medical College, both in New York, said that rheumatologists “are a little bit hesitant” to use newer agents rather than existing therapies, and have existing guidance from the American College of Rheumatology (ACR) on treating the condition.
“I think when someone has something like lupus nephritis that’s so serious, rheumatologists pull for the tried-and-true drugs that we know will affect the inflammation quickly and get that patient to remission,” she said.
Dr. Donald Thomas Jr
Donald E. Thomas Jr., MD, of Arthritis and Pain Associates of P.G. County in Greenbelt, Md., said he was surprised there was a lack of case studies on voclosporin or belimumab for lupus nephritis, but pointed to the time and cost of publishing a case report and the rheumatologist shortage as potential reasons.
“Most community-based rheumatologists such as myself are too busy,” he said. “Why we are not getting case series from major medical centers, I am not sure.”
When this news organization asked GlaxoSmithKline (GSK) if the company tracked data on real-world use of belimumab, a spokesperson responded that the drug “has extensive clinical efficacy and safety data, and 12 years of postapproval experience, demonstrating its efficacy in SLE to reduce disease activity in multiple organ systems, reduce severe flares, and enabling some patients to taper steroid use over time.”
The spokesperson also referenced published data where belimumab “showed improvement in lupus nephritis when compared to standard therapy alone,” and that the drug “has an established safety profile that has shown to be consistent in diverse patient populations across multiple clinical trials.”
Aurinia Pharmaceuticals did not respond when sent an inquiry on whether the company tracked similar real-world data on voclosporin use.
Prescribing experience
Despite the lack of published data on real-world use, the drugs are being prescribed, Dr. Thomas said.
“I have quite a few patients on these drugs,” he said, citing one patient with severe membranoproliferative lupus nephritis not in remission who is receiving a combination of voclosporin, belimumab, and hydroxychloroquine.
“I have had absolutely no problems getting either drug. The indications for the medicines are crystal clear,” he said.
Dr. Irene Blanco
Irene Blanco, MD, MS, professor in the department of medicine-rheumatology at Northwestern University, Chicago, said that in her experience, both voclosporin and belimumab have been easy to get for patients.
However, she noted she was seeing mostly patients with government-based insurance in the Bronx, N.Y., prior to moving to Northwestern in September 2022. Belimumab had been available from the New York State Medicaid program for indications other than lupus nephritis for some time, and the program was quick to add voclosporin once it became available. “It wasn’t hard to get at all,” she said.
Dr. Saxena noted the respective pharmaceutical companies have provided help in prescribing voclosporin and belimumab through offering patient assistance programs and navigating insurers’ prior authorization hurdles. As belimumab has been available for many years, its availability hasn’t changed, he noted. “Voclosporin has seen more formulary restrictions, but in my experience, I have been able to get the drug utilizing authorization procedures,” he said.
One issue Dr. Blazer said that she encounters is cost. According to prices obtained from drugs.com in March 2023, belimumab has an estimated annual price of $58.389.96 per patient, and voclosporin has an estimated annual price of $86,506.20 per patient.
“I tend to treat patients who can have some socioeconomic challenges, and so I think very long and hard before prescribing either of them,” she explained. “[C]ertainly in the case of voclosporin, when there are older, cheaper calcineurin inhibitors and I think I need one, I’m more likely to reach for one of the others.”
While GSK offers a patient assistance program for belimumab, which Dr. Blazer said she has used, physicians may not be aware of the program or have the resources in their offices to provide social work support for their patients.
“I have had patients who started it and … continued to have a flare and needed to go on disability or leave their jobs, and they were just too concerned with the ongoing cost burden, and so I ended up taking them off the medication for that reason at their request,” she said.
The fact that Black patients have lupus nephritis more often than White patients do, as well as greater socioeconomic barriers, points to access to care and cost as major factors in why new drugs are not being used, Dr. Blazer said. “I think that understanding how we can improve access is going to be extremely important in getting more real-world data and getting more patients treated,” she said.
Treatment preference
A chart audit recently released by market research firm Spherix Global Insights highlighted a potential treatment preference for lupus nephritis. Use of voclosporin increased among rheumatologists and nephrologists, but patients with lupus nephritis under the care of rheumatologists were more likely to be treated with belimumab than voclosporin.
Dr. Saxena said he has experience with both and doesn’t have a preference, instead using factors other than experience when deciding the best treatment for patients. “For example, if there are nonrenal manifestations such as arthritis or rashes, I may lean towards belimumab, but if a more rapid reduction in proteinuria is important, I may lean towards voclosporin,” he said.
Dr. Thomas weighs the pros and cons of voclosporin and belimumab with the patient. “With many lupus nephritis scenarios, either drug may be a good choice and it comes down to patient preference. The main scenario where I would choose [voclosporin] over [belimumab] is in patients with [proteinuria of] 3 g protein/day or more,” he said, while belimumab would be the choice for a patient with “nonrenal manifestations of SLE in addition to their nephritis.”
For other rheumatologists, comfort level with belimumab may play a role. “We always had [belimumab] and we were always using [belimumab], and so it would make sense that like we would go for a med, again, that we’re really familiar with and we use,” Dr. Blanco said.
Dr. Blanco has prescribed belimumab, but had been using tacrolimus until recently. “I’ve been using tacrolimus since 2016. I’m probably going to lean on the [tacrolimus] rather than going to [belimumab], which works, but maybe it’s not the end-all, be-all in terms of lupus,” she said.
Although she hasn’t yet prescribed voclosporin, Dr. Blazer said she had “much more experience with belimumab.
“I’ve prescribed other calcineurin inhibitors in the past, and usually for a patient who’s very proteinuric and as an adjunct to that standard of care to try to bring down the proteinuria,” she said.
With belimumab, she would consider adding it to a patient with severe disease who has failed treatment with mycophenolate mofetil or cyclophosphamide and has a recurrent lupus nephritis flare. “It’s something I can use as an adjunct, and I think that I can get some extra benefit from it, and it also tends to be well tolerated,” Dr. Blazer said.
How patients are responding
Dr. Thomas’ patients have been responding well on voclosporin and belimumab. “I was an early adopter of [belimumab] and had patients with lupus nephritis do great on it, way before the FDA approval,” he said.
For voclosporin, Dr. Thomas highlighted the “incredibly rapid” proteinuria response. “I had a patient have marked reduction in proteinuria in just 2 weeks. Proteinuria reduction is the number one predictor of long-term better outcomes,” he said.
Many patients receiving mycophenolate and cyclophosphamide do not go into complete remission, while the clinical trials for voclosporin and belimumab had significantly higher rates of complete response and faster response rates, compared with older therapies. “That is what we need,” he said.
“These drugs are game changers in the treatment of lupus nephritis. In my mind, belimumab and voclosporin should be considered the standard of medical care treating lupus nephritis patients,” he added.
Dr. Blanco said her patients appear to like and are tolerating voclosporin and belimumab well, but because there are no pregnancy data on voclosporin, she may choose belimumab or tacrolimus for patients of reproductive age who are considering starting a family.
Patients with extrarenal symptoms tend to do particularly well with belimumab, such as those with arthritis and skin rash, Dr. Blazer said. “In my experience, as an adjunct with those standard of care medications, I have been able to maintain remission in my patients,” she said.
Dr. Saxena said both medications are “important options” for lupus nephritis in patients who don’t respond to standard therapy. “As more doctors utilize each medication and additional data is published, I’d expect an increase uptake in both medications in the future,” he said.
Dr. Blazer reported being a contributor to GSK’s SLE Educators’ Network and has been a consultant for Aurinia. Dr. Saxena reported being a consultant for GSK and Aurinia. Dr. Thomas reported being on the speakers bureau for GSK and Aurinia. Dr. Blanco reported having no relevant financial relationships with pharmaceutical companies.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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