Finally, the phase 3 data were published in the Lancet!
Lupkynis (voclosporin) impressively improves lupus nephritis compared to when patients get mycophenolate plus steroids alone.
We can now read the data ourselves, and it is impressive.
Here is where I break down the numbers into easier to understand language:
Here is a link to the article itself:
Treatments are getting better and better for lupus patients. Now, if only anifrolumab (Saphnelo) can get approved ASAP!
Prof Brad H Rovin, MD, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet May 07, 2021 Online; DOI:https://doi.org/10.1016/S0140-6736(21)00578-XDOI
Which is better for lupus nephritis?
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
- Most patients studied had class III or class IV nephritis
- Steroids had to be tapered to 10 mg a day or less of prednisone by week 24
- Complete renal response (CRR, remission or close to remission) at 104 weeks was 30% on Benlysta plus mycophenolate (MMF) or cyclophosphamide + steroids versus only 20% on standard of care alone (MMF or cyclophosphamide + steroids). Cautionary note: the definition for CRR was stricter in the Benlysta trial than the Lupkynis trial, so you cannot assume that Lupkynis did better for CRR. The Benlysta trial required better kidney function results than the Lupkynis trial did.
- The odds ratio for the CRR was 1.74 meaning that patients who received Benlysta plus standard of care had a 74% greater odds of achieving a CRR compared to patients treated with standard of care alone (ie placebo). Again, remember that the Benlysta trial had a stricter definition for CRR. You cannot compare the 1.74 for Benlysta to 2.7 for Lupkynis.
- 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.
- Black patients were more likely to achieve a CRR at 104 weeks on Benlysta plus standard of care compared to standard of care alone. However, these results were not calculated in the research paper.
- 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 the IV form and the self-injectable SQ forms can be used to treat lupus nephritis.
- Much easier dosing than Lupkynis. IV form is the same as that for SLE. The SQ form is 2 injections (400 mg) weekly for 4 doses followed by 1 injection weekly after that.
- The package insert does not recommend use in pregnancy (was not studied). However, the pregnancy registry conducted for more than 10 years has thus far shown no signals for fetal problems. Some rheumatologists have used it safely during pregnancy.
- There was a question of possible increased suicides, suicidal thoughts, and worsened depression in previous IV Benlysta studies. However, in this lupus nephritis study, there were actually more of these problems in the placebo group. However, this was most likely not statistically significant.
- Proven in multiple phase III clinical trials that it is safe and effective for systemic lupus problems other than kidney inflammation. This especially is true for arthritis, cutaneous (skin) lupus, and patients with high anti-dsDNA and low C3 and low C4 levels. Though the FDA would not allow a fatigue mention (due to not having a validated fatigue measure for SLE), there was improvements in energy (and I note this in my own patients). Of note, it is even FDA-approved to treat children with SLE as young as 5 years old!
- Both were studied for 104 weeks
- People who don't like injections may not like it
- Only around 14% of the patients were black (under-recruitment of black patients is a continuing problem)
- On the surface, the Lupkynis numbers are more impressive regarding how fast proteinuria is decreased and the number of patients who go into a complete renal response (CRR). However, definitions for these goals were different in the two studies, so direct comparisons cannot be made. From experience, we do know that other calcineurin inhibitors, such as tacrolimus, can have markedly fast and profound effects on proteinuria, so it would not be surprising if Lupkynis were to reduce proteinuria faster than Benlysta. SEE MY INDEPTH DISCUSSION ON THE CRR BELOW.
- 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.
- It is a new and improved 3rd generation CNI. It is more potent than cyclosporine (another CNI) and is less likely to cause cholesterol problems than cyclosporine. It is much less likely to cause diabetes compared to the CNI called tacrolimus. It results in such a stable, predictable drug level that blood drug levels are not needed.
- You don't have to fail other drugs 1st before using it for LN
- Most patients studied had class IV nephritis (the type with the worst prognosis)
- Amazing steroid taper! Only 500 mg IV SoluMEDROL for 2 days (many docs use 1000 mg for 3 days) followed by 25 mg a day prednisone tapered to 5 mg a day by 2 months and 2.5 mg a day by 4 months. Many, to most docs, use 40 mg to 60 mg a day after the IV steroids. So, starting with just 25 mg is phenomenal!
- Complete renal response (CRR, remission or close to remission) at 52 weeks was 41% on Lupkynis plus mycophenolate (MMF) + steroids versus only 23% on standard of care alone (MMF + steroids).
- The odds ratio for the CRR was 2.7 meaning that patients who received Lupkynis plus standard of care had a 170% greater odds of achieving a CRR compared to patients treated with standard of care alone (ie placebo).
- Lupkynis plus standard of care resulted in low urine protein levels (urine protein to creatinine ratio of 0.5 mg/mg or less) twice as fast compared to standard of care. The median time to this goal was 172 days for Lupkynis and 372 days for standard of care! "Time is kidney," we want our treatments to work as fast as possible, so this is amazing.
- 46% of black patients on Lupkynis had a CRR by 1 year compared to 16% on standard of care. In other words, three times as many black patients achieved a CRR on Lupkynis compared to standard of care! Our black patients are harder to treat and get their disease under control, so this is promising.
- Likewise, 39% of Hispanic patients on Lupkynis had a CRR at 1 year compared to 19% on standard of care (again, they typically are harder to treat, so this is promising).
- When looking at the type of LN, the worst type, class IV diffuse proliferative-- 47% of patients had a CRR at 1 year on Lupkynis, while 25% of those did on standard of care.
- It has 2 modes of action. In addition to the immunosuppressive effects, it also stabilizes podocytes, which are essential kidney cells that ensure the kidney filters (nephrons, glomeruli) are working properly and not allowing large proteins to escape from the blood into the urine.
- 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.
- Lots of pills to take daily. Most commonly 3 capsules twice daily
- Only around 9% of the patients were black (under-recruitment of black patients is a continuing problem)
- As expected for a calcineurin inhibitor, decreased kidney function and high blood pressure were the most common side effects
- However, at week 24 and week 52, there was no difference in blood pressure between patients on Lupkynis and those on placebo plus standard of care
- In those with decreased kidney function, the dose of Lupkynis was decreased as recommended in the package insert. Most patients rebounded well to normal or to their target kidney function goal. In the end, there was "no clinically meaningful differences in mean eGFR vs placebo plus standard of care."
- The next most common side effects, as expected, were gastrointestinal issues, infections, and headaches.
- Long term side effects for infections and cancer is unknown.
- Lupkynis is more expensive. The ICER estimates a yearly price of $92,000 for patients who stay on it.
- Complicated dosing. The dose should be reduced if the kidney function decreases too much, or if there is cirrhosis of the liver, or if used with drugs that affect metabolism (CYP3A4 inducers, inhibitors, and P-gp substrates)
- Numerous potential drug interactions (such as listed above). It is important to use a drug interaction program such as UpToDate.
- Blood pressure and kidney function need checked before treatment, then every 2 weeks the first month. Kidney function should be checked monthly on treatment after month 1.
- Use during pregnancy and breastfeeding not recommended.
- Benlysta was studied combined with both mycophenolate and cyclophosphamide. Lupkynis was only studied along with mycophenolate.
- More difficult to prescribe than Benlysta. Only one specialty pharmacy handles it. Must contact Aurinia Alliance for assistance 1-833-287-4642
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."
Neither is definitely any better or worse than the other!
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.
Kuglstatter A, Mueller F, Kusznir E, et al. Structural basis for the cyclophilin A binding affinity
and immunosuppressive potency of E‐ISA247 (voclosporin). Acta Crystallogr D Biol Crystallogr.
Bîrsan T, Dambrin C, Freitag DG, et al. The novel calcineurin inhibitor ISA247: a more potent
immunosuppressant than cyclosporine in vitro. Transpl Int. 2005;17(12):767‐771.
Mayo PR, Huizinga RB, Ling SY, et al. Voclosporin food effect and single oral ascending dose
pharmacokinetic and pharmacodynamic studies in healthy human subjects. J Clin Pharmacol.
Gibson K, Parikh S, Saxena A, et al; AURORA Study Group. AURORA phase 3 study
demonstrates voclosporin statistical superiority over standard of care in lupus nephritis.
Presented at: National Kidney Foundation virtual 2020 Spring Clinical Meetings; March 26‐29,
Arriens C, Polyakova S, Adzerikho I, et al; AURORA Study Group. AURORA phase 3 study
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
Askanase A, Randhawa S, Lisk L, et al. Efficacy of voclosporin across lupus nephritis
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
Don Thomas, MD, author of "The Lupus Encyclopedia" and "The Lupus Secrets"
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.
Should lupus patients use medical marijuana?
With the increasing popularity and availability of cannabis and CBD, many lupus patients are asking, "How about CBD and lupus?"
Marijuana (cannabis) and its active components (THC and CBD) has become more popular for medical treatments. As of this writing (April 2021), 42 states in the US allow the use of medical marijuana, and 11 states (and the District of Columbia) have fully legalized its use recreationally. Many of my patients ask about using it, so I think it is important to go over some important information about it.
My goal is to present the facts based on scientific evidence without bias.
Cannabinoids are the active compounds of the cannabis plant. There are over 140 different cannabis-derived cannabinoids known, and each acts differently in the body. The 2 most studied and well-known are cannabidiol (CBD) and tetrahydrocannabinol (THC). THC is the cannabinoid responsible for the “high,” intoxicating effects with recreational users. CBD does not make people “high.”
A potential new drug for lupus--
here are some early facts
I received this email today, 4/18/21, announcing the brand name!
I have never seen a brand name announced before official FDA-approval.
Someone must know something I do not know ... did they get wind of a pending nod from the FDA?
This drug has impressive results from its research studies ... let me share a few so all SLE patients who have failed other medications realize that there is HOPE!
Research results "in a nut shell" in easy-to-understand language
The clinical trials for anifrolumab were called the TULIP trials
TULIP comes from the full research study name: Treatment of Uncontrolled Lupus via the Interferon Pathway
How does it work?
Most (70%) of systemic lupus erythematosus (SLE) patients have high levels of interferons
Interferons cause inflammation of organs, leading to permanent organ damage
Anifrolumab competes with interferon by attaching to the attachments (receptors) on immune system cells
Normally, when interferons bind to those receptors, the immune system cells become more active
Then they alert more immune system cells to become more active and attack body organs
Anifrolumab decreases this cascade of events from happening
This leads to less inflammation
It is a biologic monoclonal antibody, so it will be expensive!
Anifrolumab (Saphnelo) works differently than any drug used in the past to treat lupus!
1st in its class!
How is it given?
Saphnelo is given intravenously (IV), 300 mg, every 4 weeks (I suspect it will be 300 mg)
What were the research results?
There was a 90% reduction of interferons at 6 months in the patients who started off with high levels
Other labs measuring lupus inflammation improved (anti-dsDNA, C3, C4, CH50)
Low white blood cell counts and low platelet counts improved
What other good things did it do for the SLE patients?
They had less disease activity
Even patients who started with normal interferon levels overall improved
In TULIP-2: 57% (46 placebo vs 72 anifrolumab patients) more patients who started with high interferon levels met the primary endpoint with anifrolumab
... 58% more patients! Impressive!
When looking at all patients, a 51% higher number of patients responded to anifrolumab, including those with normal interferon levels!
You do not have to have high interferon levels to respond!
Close to twice as many patients were able to decrease their steroids to goal (25 placebo vs 45 on anifrolumab)
Lower steroids is important because higher doses of steroids cause organ damage
Anifrolumab reduced lupus flares
It especially worked well for cutaneous lupus
Look at the picture above from one of the studies
This patient had an amazing improvement. Many others did just as well
They measured skin activity with a CLASI score and looked for more than a 50% improvement
CLASI stands for Cutaneous Lupus Erythematosus Disease Area and Severity Index
Twice as many anifrolumab patients responded compared to placebo!
The numbers were 25% of the placebo cutaneous lupus patients responded, while 49% on anifrolumab did
How fast does it work?
Reduced disease activity was seen as early as 2 months
What were the side effects of anifrolumab
When comparing side effects, it is important to know that the placebo patients were not truly "placebo"
They were receiving standard of care therapy
In other words, most were on immunosuppressants and steroids that cause side effects themselves
The patients on anifrolumab were also on immunosuppressants and steroids
Therefore sorting out what anifrolumab may do vs the other drugs is very difficult
But, here are the numbers (combination of three different anifrolumab research studies):
Around 87% of anifrolumab patients and 80% of placebo patients had side effects
This include nuisance, mild side effects
The most common were viral upper respiratory tract (URI) and throat infections (cold-like infections)
Infusion reactions were the other most common
For example, 10% of the placebo (standard of care) patients had URIs, 18% on anifrolumab did
This is not surprising, interferon is important for fighting viral infections
Shingles occurred in around 6% of anifrolumab patients and 1%-2% of placebo patients
Again, not surprising since shingles is due to chicken pox virus
(MAKE SURE TO GET A SHINGLES VACCINE, SUCH AS SHINGRIX, BEFORE TREATMENT!)
6% of anifrolumab patients had to stop treatment due to side effects; 3% of placebo patients had to stop
What patients were not studied?
Patients with severe kidney inflammation (lupus nephritis, LN), brain, and nerve lupus (neuropsychiatric) were not
Therefore, we do not know if it works in them
However, I will go out on a limb and predict it will help LN patients
We know that interferon plays a role in LN
Just because we do not have study results for severe LN patients, this does not mean it does not work
What could possibly keep the FDA from approving it?
In the first TULIP-1 trial, it did not meet its primary endpoint (research goal called the SRI-4)
This could get some voting members to vote "no" for approval
However, lupus experts realize how hard it is to prove that lupus drugs work
They evaluated how the drug performed in the 1st trial
Patients did have significant improvements
They were able to lower their steroids and there was marked improvements in cutaneous lupus
One criticism is that some patients changed their NSAID (like ibuprofen) during the study
These patients were automatically labeled as a drug failure, though many of them had great responses
So they changed the primary endpoint for TULIP-2 based on their analysis of TULIP-1
The TULIP-2 trial did meet its primary end point
- Impressive results, especially for skin lupus
- Low rate of side effects (colds, sore throats, infusion reactions, shingles are the most important)
- Get your Shingrix shot before treatment
- I have a list of SLE patients who have failed everything who need to try this drug if it is FDA-approved!
Good luck to AstraZeneca who is the manufacturer of Saphnelo
Furie R, Khamashta M, Merrill JT, et al.; for the CD1013 Study Investigators. Anifrolumab, an anti-interferon-alpha receptor monoclonal antibody,in moderate-to-severe systemic lupus erythematosus.Arthritis Rheumatol. 2017;69(2):376–86.
Furie R, Morand EF, Bruce IN, Manzi S, Kalunian K, Vital EM, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1(4):e208–19.
Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, et al.; TULIP-2 Trial Investigators. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020;382(3): 211–21.
Tanaka Y, Takeuchi T, Okada M, Ishii T, Nakajima H, Kawai S, et al. Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus: a multicenter, phase 2, open label study. Mod Rheumatol. 2020;30(1):101–8.
Eating properly is important when you have lupus
Slides above and below posted with permission of Dr. Monica Guma, MD (principal investigator of this research study. The reference is at the bottom)
At the American College of Rheumatology (ACR) meeting NOV 2020, Dr. Monica Guma of UCSD reported results of using an anti-inflammatory diet in the autoimmune disease, rheumatoid arthritis (rheumatoid arthritis). She used the diet posted above.
This is pertinent for lupus patients because lupus is also an autoimmune disease. Note that there are some anti-inflammatory diet studies in lupus mice and lupus humans that show positive effects. However, we need larger, bigger studies. This study is a step in the right direction (even though it is with RA instead of lupus).
She chose motivated RA patients. They stayed on their medications as well. They followed the above diet. They had to have active RA to enter the study. Disease activity was measured 2 weeks before the study, at the start of the study, then 2 weeks later. The bacteria in their stool (microbiome) was also measured!
Below is an example of a typical day of eating:
After 2 weeks on the diet, there was improved disease activity (overall) with less tender and swollen joints.
Disease activity (measured by a research tool called the CDAI) was significantly decreased.
Below are the results after 2 weeks on the diet.
For the scientific minded... note the great "p values" for some of these measurements on the right.
After 14 days, those RA patients who did better (had lower RA disease inflammation) on the anti-inflammatory diet ended up with a greater diversity of their microbiome. This suggests that the diet influenced their gut bacteria types as well as improved disease activity.
This adds evidence that we may be able to alter our gut bacteria with diet plus improve disease activity in autoimmune diseases! There is hope that diet could also possibly help other autoimmune diseases, such as lupus, in a similar way.
We absolutely need more research. Thanks to Dr. Guma and her team for helping to pave the way for more research on diet and autoimmune disorders. Below are her results of the microbiome changes in the study.
This is my commentary:
Some of the recommendations of Dr. Bustamante (first two pics above) have quite a bit of research supporting their use (eating foods high in omega-3, avoiding omega-6, eating prebiotics) in autoimmune diseases such as lupus.
However, others have significantly less evidence (for example, avoiding solanaceae, which is nightshade plants, and eating gluten-free).
I suspect the latter food groups were included since these changes "may possible reduce inflammation."
We all look forward to more studies in autoimmune disorders, such as lupus.
Click on COMMENTS above
What have you found to be helpful in an anti-inflammatory diet?
What do you recommend for a beginner?
Do you recommend any particular books that you found to be most helpful?
Don Thomas, MD author of "The Lupus Encyclopedia" and "The Lupus Secrets"
Bustamante MF, et al. Contemp Clin Trials Commun 2020
Guma M, et al. Trial of diet to improve RA and impact on the microbiome. Presented at ACR Convergence 11/9/2020.
We have 3 drugs that are vying for FDA approval soon: Benlysta (belimumab) for lupus nephritis, voclosporin for lupus nephritis, and anifrolumab for systemic lupus erythematosus (SLE). All three were successful in the final research studies (called phase 3 clinical trials). In medical-speak, we say that "they met their primary endpoints."
My (Don Thomas, MD) prediction:
Though meeting the primary endpoints in phase III clinical trials never guarantees FDA-approval (many do not), these did so well, I predict they will be the next 3 FDA-approved therapies! They all did so well, along with having excellent safety profiles (low side effects for the amount of benefits they provided).
SHARE this with all lupus patients. Everyone needs some optimism.
Why is this so joyous? In March 2011, Benlysta was the very first FDA-approved drug for lupus since President Eisenhower was president (it took over 50 years!). That is a travesty. However, the approval of Benlysta showed pharmaceutical companies that it was worth their time, effort, and money to actively research lupus in more depth and that drugs could be proven to be helpful in treating SLE. And now... we have possibly 2 new drugs just around the corner (voclosporin and anifrolumab)? Yes, it is time to rejoice, hope, and pray that the FDA finds the research results to be as good as they appear.
This post, though, is all about Benlysta. Just this week, the New England Journal of Medicine published the positive results of their research study called BLISS-LN (Link to the study is below). This stands for "BeLImumab in Subjects with SLE with Lupus Nephritis study." It showed that Benlysta is effective for lupus nephritis.
Let's 1st briefly discuss lupus nephritis ...
This is why rheumatologists ask to see their patients every 3 months. We want a urine sample to evaluate and make sure our patient isn't getting lupus nephritis. When I see it as a possibility, I pounce on it and treat it aggressively. Using this approach, my only patients who have gone into kidney failure and dialysis, and then kidney transplantation were my patients who were poorly adherent to their therapy. By the way, don't let that happen to you!
Read and abide by my Lupus Secrets. If you follow them, you'll successfully fight your lupus.
They had 224 patients in the placebo group and 224 patients on Benlysta. However, it wasn't really placebo. The "placebo" group was getting standard of care (steroids plus either cyclophosphamide or CellCept, mycophenolate). Those who received Benlysta had their Benlysta in addition to the "standard of care."
It had some impressive results after 104 weeks:
30% of the Benlysta group had a complete response to therapy while 20% of the placebo group did. That is 50% greater in the Benlysta group compared to standard of care plus placebo group. This is impressive. The "placebo group" is how we currently treat lupus nephritis patients! Imagine getting a 50% higher response rate by adding another medicine.
By the way, you may think, well an additional drug! That could mean more side effects. Guess what? ... Serious adverse events occurred in 30% of those on standard of care treatment plus placebo, while 26% of those on Benlysta plus standard of care had serious side effects. This is actually less in the Benlysta group. However, that does not mean that Benlysta causes less side effects. This is actually not statistically significant.
Also, don't think this is "horrible" that 30% of patients had "serious adverse events." Guess what would have happened without these treatments? ... virtually 100% serious adverse events would have occurred due to the lupus nephritis leading to kidney failure, dialysis, kidney transplantations and deaths. (the benefits of the medicines greatly outweigh their potential side effects compared to this).
By the way, there were other impressive positive results in the study, but I wanted to hone in on the "complete renal response" result above.
Remarkably, there were only 3 deaths (2 on placebo, 1 on Benlysta), only one patient went into complete kidney failure (a placebo patient). Impressive when you realize how horrible the alternative without treatment would have been.
I've been using Benlysta since 2011, and I have many SLE patients who are in low disease activity and remission after failing other treatments. This includes quite a few lupus nephritis patients. In my experience, it is one of the safest medicines we have for SLE. Plaquenil is probably the only safer drug.
It comes in two forms of dosing ... a self injectable every other week form, or a monthly IV (intravenous form). According to UpToDate.com, the self-injectable form costs close to US$ 30,000 a year. The IV form is more expensive (nurses, IV equipment, etc.)
So some big, important questions are:
Which patients will benefit the most?
Can we figure out which patients are at highest risk for not responding completely to standard of care therapy (CellCept and cyclophosphamide)?
If we could figure this out, then those patients should be the ones who get it.
It will be interesting to see what happens if it gets FDA-approved for lupus nephritis. I cannot imagine it not getting FDA approval, by the way. The study was that impressive.
Bottom Line?: Lots of exciting stuff happening in lupus!
Please COMMENT in "LEAVE A REPLY" below.
Are you on Benlysta? How are you doing? What is your experience like? Do you have lupus nephritis? How have you done?
I love giving good news!
- Don Thomas, MD
P.S. Remember to download my Lupus Secrets to learn more!
Reference: Furie R, et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. NEJM SEP 2020;383:1117-1128
Disclosure: I am on the Speaker's Bureau for GSK, maker of Benlysta. This is the only pharmaceutical Speaker's Bureau I am on. I truly believe in Benlysta as being a great therapy for SLE patients. It is not for everyone, but many do great on it.
Don Thomas, MD
I specialize in taking care of patients with systemic lupus. I enjoy sharing helpful, practical information for them to use and be better able to live with and successfully fight against their disease. Make sure to read and follow my Lupus Secrets
DONALD THOMAS, MD
Complementary Alternative Medicine
COVID 19 And Lupus
COVID-19 And Lupus
Diet And Lupus
Flares In Lupus
Infections And Lupus
Kidneys & Bladder
Labs Used In Lupus
Nails And Lupus
Remission And Other Disease Activities
Symptoms In Lupus
Triggers Of Lupus Disease Activity