‘Comfort level’ driving divide between rheumatologists, nephrologists in lupus nephritis
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Recent data has revealed a growing divide between rheumatologists and nephrologists in their therapeutic choices for patients with lupus nephritis, according to researchers from Spherix Global Insights.
The data suggest rheumatologists prefer belimumab (Benlysta, GlaxoSmithKline), which was approved for lupus nephritis in late 2020, while those in nephrology are more likely to choose voclosporin (Lupkynis, Aurinia), which received the go-ahead in the same population in early 2021.
According to Ryan Rex, insights director of rheumatology at Spherix, the difference in prescribing habits comes down to “comfort level.”
“Rheumatologists have been using Benlysta for over a decade, since it was approved in March 2011 for SLE,” he said. “This gives them a built-in comfort level with this biologic.”
The Spherix data are based on 17 months of tracking the two drugs, using monthly performance benchmarking with quarterly reports to “understand perceptions of each brand, their evolving places in the treatment paradigm, and projections for future use,” according to a statement.
In addition, Spherix researchers collaborated with 50 nephrologists and 50 rheumatologists in the United States, who discussed their impressions of the drug and their experiences using them each month.
According to Rex, belimumab’s approval for lupus nephritis served to give the drug “a lift” with rheumatologists overall.
“They perceive Benlysta to be safer than the new calcineurin inhibitor Lupkynis and rate Benlysta higher on risk- and cost-benefit performance metrics, saying the drug has the greatest overall benefit to lupus nephritis patients when assessing the two drugs head-to-head.”
Richard Furie, MD, chief of the division of rheumatology at Northwell Health, and professor of medicine at Hofstra/Northwell School of Medicine, in New York, also used the phrase “comfort level” when discussing nephrologists’ preference for voclosporin. However, there are other reasons why these clinicians prefer the drug.
“Lupkynis has a fast onset of action in reducing proteinuria,” Furie said.
The oral formulation of voclosporin is another attractive feature for some patients and practitioners, he added.
Digging into these features and understanding what both rheumatologists and nephrologists have to say about these two drugs may provide insight on management of this complicated patient population.
‘Significant pill burden’
Although oral formulations are often seen as a plus for any drug, there was not universal consensus on this point for belimumab, according to Rex.
“It should be noted, however, that quite a few rheumatologists actually prefer intravenous infusions for their patients as they can more easily monitor a patient’s compliance with their treatment regimen,” he said. “It allows them to have a clear record of drug infusions versus an oral drug where the patient’s skipped dosing may go unnoticed.”
Conversely, support of the oral formulation of voclosporin is also not universal. The issue is that the maximum dose can involve as many as three pills twice a day, according to Furie.
“This is a significant pill burden,” he said. “It definitely leads to compliance issues.”
Factor in the pill burdens associated with other medications used in lupus nephritis, like hydroxychloroquine or mycophenolate mofetil, and patients are simply unwilling or unable to take all of those pills on any given day.
“It could be that as many as 20% or 30% of patients are not taking some of their drugs,” Furie said.
If there is an advantage of voclosporin that carried more universal agreement, it is the rapid onset of action.
“It is quite important to have quick onset of medications to protect kidney function in patients with lupus nephritis and prevent an irreversible damage to the renal tissue that could lead to chronic kidney disease progression,” Shivani Garg, MD, MS, assistant professor in the department of medicine, rheumatology division, at the University of Wisconsin School of Medicine and Public Health.
Rex dug deeper.
“Lupus nephritis is a progressive disease and can flare, so particularly with more severe lupus patients, and those experiencing high levels of proteinuria and/or precipitous renal function decline, it is important to get those issues under control and the patient stable as quickly as possible,” he said. “Lupkynis presents an option to achieve results more quickly, particularly in severe or refractory cases.”
Although Furie generally agrees that voclosporin has a faster onset of action, he urged caution in interpreting the data sets that led to the approval of the two drugs.
“People are tempted to compare the two studies, but they had two different designs, two different study populations,” he said. “Separation occurred between placebo and Benlysta at 6 months.”
Data show that somewhere between 10% and 30% of patients with lupus nephritis progress to end-stage renal disease requiring dialysis or, eventually, transplant to prolong their lives, according to Rex.
“Slowing disease progression is critical,” he said.
‘Perceptions colored by comfort level’
Acknowledging that rheumatologists prefer belimumab and nephrologists prefer voclosporin is important to making sense of therapeutic choices and improving patient care, according to Rex. “Again, we see perceptions colored by comfort level and previous use of the drug class,” he said. “Nephrologists are much more comfortable using calcineurin inhibitors like tacrolimus and cyclosporine in kidney transplant patients, for example, so they know the drug class well.”
Simply put, many nephrologists are unfamiliar with belimumab, at least in part because they are not accustomed to intravenous infusions, as rheumatologists are. However, even voclosporin has an advantage over other drugs in the class.
“Unlike other calcineurin inhibitors, like tacrolimus, a physician does not need to monitor its levels,” Garg said of voclosporin. “Thus, overall, it is easy to use and does not require additional drug level monitoring. However, given high rates of medication nonadherence in lupus, it remains unclear if not monitoring drug levels is a pro or a con for Lupkynis.”
Rheumatologists, on the other hand, are very accustomed to coordinating the approval and administration of biologics in a range of rheumatic conditions.
“Nephrologists give the edge to Lupkynis over Benlysta particularly on patient adherence, efficacy and tolerability,” Rex added. “Interestingly, however, in terms of overall calcineurin use in lupus nephritis patients, rheumatologists are more likely to use Lupkynis whereas nephrologists prescribe generic calcineurin inhibitors more frequently.”
Despite this trend, Furie noted that some rheumatologists who focus on lupus nephritis have gained familiarity with tacrolimus and other calcineurin inhibitors.
It seems likely that the trends in prescribing will continue to shift as both drugs spend more time on the market. The good news is that both rheumatologists and nephrologists now have options for minimizing steroid doses in their patients.
‘Powerful tool’
Most rheumatologists understand the delicate line to be walked when it comes to steroids.
“High cumulative dose of steroids is linked with several poor outcomes in patients with lupus and lupus nephritis, such as cardiovascular disease events, cataracts, avascular necrosis, adrenal insufficiency, infection and poor wound healing risk, fractures and bone loss,” Garg said.
It is for this reason that current guidelines and recommendations underscore the need to control lupus nephritis adequately with steroid-sparing agents and taper steroids accordingly, Garg added.
However, it is also true that steroids remain a “powerful tool” in treating lupus nephritis, according to Rex, even as he acknowledged their safety profile.
“Steroids are associated with fluid retention, hyperactivity, stomach upset, mood issues, and even rarer but more serious issues like certain types of cancer,” he said. “All of this leads physicians to approach the use of these drugs much more cautiously than in the past.”
Which is why both belimumab and voclosporin have been welcome additions to the armamentarium, Rex added.
“Rheumatologists and nephrologists alike cite the steroid-sparing effect of the two new lupus nephritis drugs as reasons for prescribing the agents and they note measurable results,” Rex said. “The drugs work to control disease activity and allow them to modulate the disease, thus allowing them to reduce their patients’ overall steroid burden.”
If there is another factor in the conversation, it pertains to which patients may be best served by which drug.
Shifting trends
“Patients with moderate lupus, and some patients with moderate-to-severe disease, can benefit from Benlysta as an add-on therapy to treat not only the symptoms and manifestations of their lupus — like uncontrolled skin and joint disease — but also their lupus nephritis, to help preserve their renal function,” Rex said. “With the lupus nephritis indication in addition to SLE, many physicians deem this drug as having a broader application in lupus overall.”
That said, belimumab may not be what physicians reach for in more severe or refractory lupus nephritis cases where a more immediate effect is required, he added.
“With these two options, rheumatologists may hold onto lupus nephritis patients longer than in the past, as opposed to referring them to nephrology,” Rex said. “They may take increased ownership of prescribing and patient care in co-management scenarios.”
Furie once again brought the conversation back to the interpretation of data.
“The rheumatology community in general has gotten used to fairly robust effect sizes in diseases like RA and PsA, but here you are looking at very modest effect sizes,” he said.
Some clinicians, then, may be cautious about using these drugs, particularly because they are expensive.
“But if you can modify renal disease in one out of five to 10 patients, you are ahead,” Furie said.
Reference:
Spherix press release, “Spherix Research Reveals Rheumatologists Taking the Lead Over Nephrologists in Both Benlysta (GlaxoSmithKline) and Lupkynis (Aurinia) Patient Initiations in Lupus Nephritis.” Link: https://www.prnewswire.com/news-releases/spherix-research-reveals-rheumatologists-taking-the-lead-over-nephrologists-in-both-benlysta-glaxosmithkline-and-lupkynis-aurinia-patient-initiations-in-lupus-nephritis-301569917.html.
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