Which is better for lupus nephritis?
Here is my answer!
– The specifics on the complete renal responses Benlysta vs Lupkynis
– Included information on extra renal lupus
– Included information about the long term extension trial to 104 weeks with Lupkynis
Background on lupus nephritis:
– Systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system attacks the person’s own body.
– Around 40% of the time, it will attack the kidneys. This is called lupus nephritis (LN).
– It causes no symptoms whatsoever until it is severe and permanent damage is already occurring. This is why we ask our SLE patients to give a urine sample every 3 months to look for increased protein in the urine (proteinuria) as a sign of nephritis.
– Up to recently, our treatments have not been very good, with around 15% of our patients going into kidney failure by 10 years after their diagnosis. Then they need dialysis or a kidney biopsy. This is one reason why we need better treatments. “Standard of care” with mycophenolate and cyclophosphamide are NOT good enough.
– Our goal in treating LN is to get it into remission.
– Numerous drugs have been studied this past decade, trying to find better treatments. In those studies, only 22% to 32% of patients go into remission on the usual treatments of mycophenolate or cyclophosphamide. Remission is so important because this is the best way to prevent kidney failure and death.
– A kidney biopsy is essential to help figure out what to do. After numbing up the back under the ribcage, a tiny needle is inserted to grab a tiny piece of kidney. We then look at it under the microscope.
– Above are two examples of kidney biopsies as seen under the microscope.
– Note the normal kidney top right. The glomerulus (nephron) is one of millions of tiny filters in our kidneys. Note all the white spaces. These white spaces are essential for waste products to fill up and flow into the urine.
– Now look at the LN kidney on the bottom affected by the worst form called “class IV diffuse proliferative nephritis.” Note how there is hardly any of the large white spaces that you see in the normal glomerulus. This filter (glomerulus) is unable to filter out waste products. Without good treatment, this patient would absolutely go into complete kidney failure.
December 17, 2020: Benlysta (belimumab) was the 1st FDA-approved drug to treat adults with lupus nephritis (LN) when added on top of standard of care (high doses of steroids plus either mycophenolate or cyclophosphamide)
January 21, 2021: Lupkynis (voclosporin) was the first oral drug FDA-approved to treat adults with LN when added on top of standard of care (high dose steroids plus mycophenolate)
May 5, 2021: Benlysta is approved to treat adults with LN in the European Union!
So, which is better? Benlysta or Lupkynis?
I think that is best answered by looking at the pros and cons of both drugs:
Data below is from the phase III clinical trial (BLISS-LN) unless otherwise stated
– Flexible options. Given both by IV (intravenous) by a nurse, or at home by self injection (SQ form).
– Has been around and used for a long time (since March 2011), so there is a lot of experience with its safety and effectiveness
– Its safety in the lupus nephritis trials was similar to its safety in the phase III clinical trials for SLE.
– You don’t have to fail other drugs 1st before using it for LN
– Patients receiving Benlysta plus standard of care had a 58% increased likelihood at any time of achieving a CRR and remaining in a CRR until week 104. Note that this timing cannot be compared to Lupkynis’ timing for decreased proteinuria. These are two different measurements.
- Benlysta plus standard of care resulted in a 49% lower likelihood of a “renal-related event or death” up to week 104 compared to placebo plus standard of care treatment.
– Benlysta was studied combined with both mycophenolate and cyclophosphamide. Lupkynis was only studied along with mycophenolate.
– Excellent patient assistance program at www.benlysta.com.
- Both were studied for 104 weeks
– Only around 14% of the patients were black (under-recruitment of black patients is a continuing problem)
- It is expensive. But not as expensive as Lupkynis. The ICER (Institute for Clinical and Economic Review) estimates a yearly price of $43,000 for patients who stay on Benlysta.
Data below is from the phase III clinical trial (AURORA trial) unless otherwise stated
– Oral capsule form. Not an injection.
– It is brand new with no long term data. However, it is in a class of drugs called calcineurin inhibitors (CNI) which have been around for a long time.
– Excellent patient assistance program, Aurinia Alliance. They will get medication in the patient’s hands within 5 days if there is any delay in getting it while they help work on the prior authorization process: support@AuriniaAlliance.com and 833-287-4642
– It is not FDA-approved to treat SLE problems other than lupus nephritis. However, in both the phase 2 and phase 3 clinical trials, there were some numerical improvements in a lupus disease measurement called the SELENA-SLEDAI score. The lupus nephritis trials were not designed to answers this question. I hope Aurinia pharmaceuticals considers doing an SLE study.
– Although the phase III clinical trial was only 52 weeks, a press release in May 2021 stated that low urine protein levels along with stabilization of kidney function was seen through week 104 in the long term extension trial.
Why is a complete renal response (CRR) so important? Our goal in treating lupus nephritis is to get it into remission. Patients who reach remission are much less likely to go into kidney failure, have less organ damage, and live significantly longer than patients who have a partial response to therapy. CRR is not called “remission” because you truly do not know if the patient is in remission unless you do a kidney biopsy, but it is the closest we have without the biopsy.
First, what did they have in common? – Both did not allow any significant increase in steroids, change in doses of ACEi’s or ARBs (blood pressure medicines that lower urine protein), addition of an antimalarial if not on one already, and no addition of any other immunosuppressant drug.
The other is they both had a similar urine protein to creatinine ratio (UPCR) goal (with one slight, nonsignificant difference). Lupkynis patients had to reach a UPCR of 0.5 mg/mg or less; Benlysta patients had to be below 0.5 mg/mg.
The big difference for complete renal response was in the kidney function stabilization criteria:
Benlysta required a eGFR of 90 ml/min or higher (or within 10% of the baseline if less than 90).
Lupkynis patients could have a eGFR of 60 ml/min or more (or within 20% of the baseline if less than 60).
It is much more difficult to have an eGFR of 90 ml/min or higher when you have severe lupus nephritis. So, this was an impressive requirement.
However, this is balanced out by Lupkynis using the CRR as its primary endpoint, while Benlysta used it as a secondary endpoint. Having it as the primary endpoint is wonderful as that is truly our goal. We don’t just want a “renal response,” with a treatment, we want remission (CRR or close to a CRR).
INTERESTING FACT ABOUT LUPKYNIS AND PREGNANCY:
Other calcineurin inhibitors (such as tacrolimus) are safe to use in pregnancy.
Why is it recommended not to use Lupkynis in pregnancy?
Each capsule of Lupkynis contains 21 mg of alcohol.
Putting it into perspective, 5 oz of red wine contains around 4000 mg of alcohol.
However, the Centers for Disease Control states, ” There is no known safe amount of alcohol use during pregnancy or while trying to get pregnant.”
And the answer is (Benlysta vs Lupkynis) …
They are both game changers in the treatment for lupus nephritis, and they both have their place
What would I do if I had severe lupus nephritis?
Whenever I treat a patient, I always put myself in their shoes and ask myself, “what would I want if I were the patient, knowing everything that I know?” Or, what would I recommend to my family member if they were the patient.
The problem with the treatments for lupus nephritis prior to Benlysta and Lupkynis is that most patients do NOT go into remission.
Previous therapies (called “”standard of care” in the research studies) take too long to work. While we wait for them to work, permanent damage to the kidneys occurs. Once you lose each nephron (filter) due to lupus inflammation, it is gone forever.
We end up having to use too much steroids which cause side effects in everyone when used at high doses for lupus nephritis. These high doses of steroids also cause organ damage themselves. We always want to get away from treatments that also cause damage to our bodies!
So here we have two drugs that have proven themselves to increase remission, work faster, and decrease the need for steroids.
Plus, they had excellent safety in the studies. In my opinion, they are markedly safer than steroids.
If I had lupus nephritis, I would absolutely want Benlysta or Lupkynis plus mycophenolate plus hydroxychloroquine plus an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker plus vitamin D plus religious sunscreen usage immediately as my treatment.
If my nephritis were severe, I’d only want 250 mg to 500 mg IV pulse SoluMEDROL for only 2 days followed by just 20 mg to 25 mg a day of prednisone daily with a rapid taper. I want as little of steroids as possible.
I would also see if my insurance would allow me to use both Benlysta plus Lupkynis at the same time! They work in 2 different directions and if they could get me into remission faster and get me off steroids faster, why not?
What should you do if you have lupus nephritis?
– Learn as much as you can. Knowledge is Power!
– Mentally accept the fact that you will need to take numerous medications to treat the nephritis. Take all the medicines religiously. When you get tired of taking your medicine, tell yourself, “I want to do everything possible to stay off dialysis and prevent needing a kidney transplant.” Each treatment has its reason behind using it. Your goal is to let the other meds (Hydroxychloroquine, vitamin D, sunscreen, mycophenolate or cyclophosphamide, Benlysta, Lupkynis, ACEi or ARB) do their magic so you can get under control faster and get down and off of those steroids! Just for example, I recently started taking care of this very nice gentleman with severe lupus nephritis who had numerous, painful, broken bones in his spine from steroids (his treatment did not include all the things I mention above). I wish I could have taken care of him from day #1. I’m confident I could have helped prevent that from happening. Don’t let that be you.
– If you want an easy to take medicine that has proven long term safety, and is less of a hassle to take, then Benlysta may be a good choice for you.
– If you think that Lupkynis may work faster and better (we do not know this 100%, however), then Lupkynis may be a good choice if you don’t mind taking 6 capsules daily and getting frequent blood pressure and blood work done.
– If you want to give it everything possible (like I would) ask your doctor about taking both.
PLEASE COMMENT above. Would you add any other pros or cons? What are your questions about lupus nephritis, Benlysta, and Lupkynis?
Package inserts for both Benlysta and Lupkynis
Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB, Saxena A, Green Y, Ji B, Kleoudis C, Burriss SW, Barnett C, Roth DA. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med. 2020 Sep 17;383(12):1117-1128. doi: 10.1056/NEJMoa2001180. PMID: 32937045.
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immunosuppressant than cyclosporine in vitro. Transpl Int. 2005;17(12):767‐771.
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pharmacokinetic and pharmacodynamic studies in healthy human subjects. J Clin Pharmacol.
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demonstrates voclosporin statistical superiority over standard of care in lupus nephritis.
Presented at: National Kidney Foundation virtual 2020 Spring Clinical Meetings; March 26‐29,
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demonstrates voclosporin statistical superiority over standard of care in lupus nephritis.
Presented at: EULAR European E‐Congress of Rheumatology 2020; June 3‐Sept 1, 2020
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biopsy classes: pooled data from the AURORA 1 and AURA‐LV trials. Presented at:
National Kidney Foundation virtual 2021 Spring Clinical Meetings; April 6‐10, 2021.
Rovin BH, Parikh SW, Huizinga RB, et al; AURORA Study Group. Management of lupus nephritis with voclosporin: an
update from a pooled analysis of 534 patients. Presented at: American Society of Nephrology Kidney Week 2020
Reimagined; Oct 19‐25, 2020
Caster DJ, Solomons N, Randhawa S, et al; AURORA Study Group. AURORA phase 3 study demonstrates voclosporin
statistical superiority over standard of care in lupus nephritis. Presented at: ERA‐EDTA Virtual Congress; June 6‐9, 2020
DISCLAIMER: I am on the Speaker’s Bureaus for both Benlysta and Lupkynis. I do this proudly as I believe strongly in how much these medications can improve the treatment of our lupus patients, helping them live longer, better lives. I hope you can agree that the information I presented above is unbiased, using the data from the research studies. However, the opinions expressed in what I would want for treatment and what I recommend for patients are my opinions, based upon the research results.