Treatment of Lupus: Best Practices and Guidelines
posted in Drugs used in lupus on December 29, 2024 by
Updated January 3, 2025
The treatment of lupus has improved significantly over the past decade. Most patients can expect to go into remission or low-disease activity with proper treatment. Advancements that have made a big difference include new FDA-approved drugs (Saphnelo, Benlysta, and Lupkynis). There are also better laboratory tests like hydroxychloroquine drug levels, and CB-CAPSs.
In 2023 and 2024, formal guidelines by lupus experts were published. These are best practices that all rheumatologists should consider following. Below are some highlights from these guidelines. I included some personal comments on my thoughts about these recommendations.
I feel strongly that treating lupus should be a team approach between the patient and the treating physician. The more patients educate themselves on “best practices,” the better you can discuss options with your doctors.
Guidelines for The Management and Treatment of Lupus
In 2023, the European Alliance of Associations for Rheumatology (EULAR) published guidelines for SLE management that ensure much better treatment of lupus. World experts scoured the best medical literature and research to develop the best ways to treat SLE. I agree with their recommendations.
Some key points, including comments by me, are as follows:
All SLE Patients Should be Treated with an Antimalarial (like hydroxychloroquine)
Antimalarial drugs have numerous benefits with relatively low side effects. Hydroxychloroquine is the only drug proven to prolong survival in SLE while also reducing organ damage and increasing remission rates.
Limit Glucocorticosteroids (Steroids)
Steroids are the fastest-working drugs for SLE and can reduce organ damage by quickly. They work by reducing inflammation while other therapies await kicking in. They can also improve quality of life (such as by reducing pain and improving energy).
IV pulse steroids can be considered for moderate to severe SLE as they help the treatment of lupus, and reduce the dose of daily oral steroids, and increase remission rates.
However, after starting steroid therapy, the goal is to get patients completely off steroids. Doses less than 5 mg daily of prednisone have even been linked to side effects like heart disease and infections. In patients who are unable to stop steroids, the goal is to limit steroid use to 5 mg prednisone daily or less, if possible.
Immunosuppressant Drugs or FDA-Approved Biologics Should be Added if Not in Remission with HCQ or if Unable to Stop Steroids
Getting patients into remission as fast as possible and tapering steroids to reduce steroid-induced side effects is very important for the treatment of lupus. These goals can be achieved faster by adding an immunosuppressant (like methotrexate, mycophenolate, or azathioprine) or a biologic (Saphnelo or Benlysta).
For Patients with Moderate to Severe Disease, Consider Including an Immunosuppressant or an FDA-Approved Biologic as Initial Therapy
Patients with moderate to severe disease are at the highest risk of developing organ damage quickly. Achieving remission as soon as possible after diagnosis is important. Also, these patients are less likely to go into remission with HCQ and get off steroids as well. Adding these medications to HCQ as initial therapy can help achieve remission and get off steroids faster compared to adding them later.
SLE Treatments Have Varying Degrees of Medical Evidence
No large, well-done head-to-head studies have proven superiority between SLE treatments. However, some therapies have better medical evidence to support their use in SLE than others. Therapies with the best evidence (termed Grade A Evidence) are the use of HCQ, belimumab (Benlysta), and anifrolumab (Saphnelo). The next level (Grade B Evidence) goes to methotrexate and mycophenolate for mild to moderate disease, calcineurin inhibitors (like tacrolimus) for moderate disease, and rituximab for severe disease. The next level (Grade C Evidence) goes to azathioprine for mild to moderate disease, and mycophenolate and cyclophosphamide for severe disease.
Drugs also have varying degrees of proof of preventing organ damage. Dr. Anca Askanase and fellow experts published their results showing hydroxychloroquine, Benlysta, and Saphnelo as having the best research behind them. Mycophenolate mofetil had the best evidence out of the oral immunosuppressants. These data should also be considered when choosing therapies. Steroids were shown to increase the risk of organ damage, providing additional evidence that their use for the treatment of lupus should be limited.
Consider Intravenous Cyclophosphamide for Organ-Threatening or Life-Threatening Disease; Consider Rituximab for Refractory Cases
Cutaneous Lupus Should be Treated with Topical Steroids, Topical Tacrolimus, Antimalarials, and/or Systemic Steroids
Antimalarials (hydroxychloroquine and chloroquine) are the oral drugs of choice for cutaneous lupus lesions too severe for topical therapies to control. Quinacrine can be added if HCQ and CQ are inadequate or used instead if there is antimalarial retinopathy.
Second-Line Medicines for Cutaneous Lupus are Methotrexate, Mycophenolate, Belimumab, or Anifrolumab
Anifrolumab (Saphnelo) has especially had impressive results for treating severe cutaneous lupus. For difficult cases, a dermatologist should be involved with management decisions. Other therapies such as dapsone, retinoids, tacrolimus, cyclosporin, azathioprine, cyclophosphamide, or rituximab can be considered. Thalidomide and lenalidomide can be considered for cases failing several drugs.
Common SLE Complications and its Treatments Should be Prevented and Treated
Preventing heart attacks, strokes, and blood clots (chapter 21), infections (chapter 22), cancer (chapter 23), and osteoporosis (chapter 24) should be proactively done. If they occur, prompt therapy should be given.
Check a Hydroxychloroquine Drug Level Every Visit
OK, I added this. However, if this were done every visit, it would check adherence to therapy and guide practitioners to adjust HCQ dosing. This ensures better effectiveness while also reducing the risk of side effects. In my practice, I now have close to 100% adherence and much higher remission rates in my clinic compared to before checking levels. My patients know HCQ works when taken, and they know I am watching them.
Make sure to check a trough whole blood level. For patients… this means waiting until after your labs before you take your dose of HCQ to ensure it is accurate.
For providers, Dr. S Garg et al recommend a target level of 750 – 1200 ng/mL to increase response rates, reduce hospitalizations, reduce health inequality problems, and reduce side effects like retinopathy. In my patients who are hard to get into remission, I aim for a level of 1000 ng/mL to 1200 ng/mL based upon the study from France that showed a four-fold lower rate of flares with levels above 1000 ng/mL.
I start treatment with 5 mg/kg/weight but then adjust my dose to hit the above target rate. I think that basing dose simply on body weight is stupid for a drug that has a 25% to 75% bioavailability.
Check Labs At Least every 6-12 months (every 3 months in those at high risk of lupus nephritis)
Check CBC, chemistry panel, urine protein to creatinine ratio, C3, C4, anti-dsDNA, EC4d in those in whom C3 and C4 are unhelpful.
____________________________________________________________________
Guidelines for Managing Lupus Nephritis
Lupus nephritis (LN) is a major cause of SLE patients not doing well. In 2024, the American College of Rheumatology (ACR) presented guidelines for the treatment of lupus nephritis. A summary of some of the important aspects, including comments by me, are as follows:
SLE Patients Should be Tested for Proteinuria Regularly
The screening test of choice for LN is a random urine protein to creatinine ratio (UPCR) performed as the 1st or 2nd void of the day. This should be ordered at least every 6 to 12 months. Many lupus experts prefer every 3 months in patients who are at increased risk of LN.
A Kidney Biopsy Should be Done Soon as Possible if the UPCR is 500 mg/mg or higher.
A kidney biopsy should also be considered at lower levels of proteinuria if anti-dsDNA, anti-C1q, or EC4d are high, or C3 or C4 are low.
Steroids Should be Used in Patients Likely to have LN Even Before Biopsy Results are Ready
HCQ Should be Used in all LN Patients
Hydroxychloroquine increases remission rates and reduces flares of lupus nephritis when used with the immunosuppressants mentioned below.
Consider IV Pulse Steroids followed by Lower than Usual Oral Daily Steroids. Tapering Below 6 mg Prednisone Daily by 6 Months.
The belimumab and voclosporin clinical trials showed that we can use lower doses of steroids than we had used in the past. IV pulse methylprednisolone 250 – 1000 mg daily for 1-3 days followed by 0.5 mg/kg/day or less of oral prednisone are recommended. The voclosporin clinical trials only used 20 to 25 mg daily of prednisone with a very rapid taper. Steroids should be tapered as quickly as possible. They should also be tolerated with a goal of being less than 6 mg daily by 6 months.
Kidney Protective Drugs Should be Added for Any Amount of Proteinuria
An angiotensin converting enzyme inhibitor or angiotensin receptor blocker should be used to reduce proteinuria and help protect the kidneys. Other renal protective drugs, like SGLT2 inhibitors should also be considered.
Triple Immunosuppressant Therapy Should be Considered as Initial Therapy in Patients with Proliferative (Classes 3 and 4) LN
High-dose steroids plus mycophenolate or intravenous cyclophosphamide (especially the low-dose EuroLupus regimen) plus either belimumab or a calcineurin inhibitor (CNI, like cyclosporin, tacrolimus, or voclosporin) should be considered as soon as a diagnosis of LN is made.
Mycophenolate is Preferred over Cyclophosphamide
For Proteinuria of 3 gm/gm or More, Triple Immunosuppressant Therapy that Includes Mycophenolate Plus a Calcineurin Inhibitor (tacrolimus, cyclosporin, voclosporin) is Preferred over Using Belimumab
To Monitor Response to Therapy: Measure Proteinuria, anti-dsDNA, C3, and C4 Every 3 Months
If Triple Immunosuppressant Therapy Doesn’t Achieve Proteinuria Goals, Therapy Should Be Adjusted
Successful treatment of lupus nephritis is defined as
- at least a 25% improvement in proteinuria by 3 months of treatment
- 50% reduction by 6 months
- a UPCR of less than 0.8 gm/gm by 1 year.
Patients who reach these goals have a greater chance of not going into kidney failure. If these goals are not achieved, adherence to therapy should be assessed, then adjusting therapy should be considered. Examples include increasing the dose of medications if not on maximum doses, changing one drug to another (e.g., changing mycophenolate mofetil to cyclophosphamide), adding a medication (like adding a CNI to triple therapy that already includes belimumab) or considering repeating another kidney biopsy.
- For Patients in Remission, Maintenance Therapy that Includes Mycophenolate is Recommended over Azathioprine
- If a Patient is not at Proteinuria Goals Using Dual Therapy (steroids plus mycophenolate or cyclophosphamide) Consider Adding Belimumab or a CNI.
- For Membranous Lupus Nephritis (class V) Less than 1 gm/gm Proteinuria, Consider Treating with Steroids +/or an Oral Immunosuppressant (mycophenolate, azathioprine, or a CNI)
- For Membranous Lupus Nephritis (class V) with 1 gm/gm Proteinuria or Greater, Consider Treating with Triple Immunosuppressant Therapy that Includes Mycophenolate Plus a Calcineurin Inhibitor
- For Patients Who Fail the Above Therapies, Consider Combining Mycophenolate Plus Belimumab Plus a Calcineurin Inhibitor, or Consider Treating with an Anti-CD20 Biologic (rituximab or obinutuzumab)
- In Patients Who Fail Therapy and Near End Stage Kidney Disease, Kidney Transplantation Should be Planned ASAP, Even Before Dialysis is Needed
___________________________________________________________________________________________________________________
For more in-depth information on The Treatment of Lupus:
Read more in The Lupus Encyclopedia, edition 2
Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia
If you enjoy the information from The Lupus Encyclopedia, please click the “SUPPORT” button at the top of the page to learn how you can help.
What are your comments and opinions?
If you have lupus, what has your experience been? What do you recommend for other patients?
Do you have any questions to ask Dr. Thomas?
Please click on “Leave a Comment” above to comment.
Please support “The Lupus Encyclopedia” blog post page
Click on “SUPPORT” at the top of the page to learn how you can support “The Lupus Encyclopedia“
For more in-depth information on Treatment of Lupus: Best Practices and Guidelines:
Read more in The Lupus Encyclopedia, edition 2
Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia
If you enjoy the information from The Lupus Encyclopedia, please click the “SUPPORT” button at the top of the page to learn how you can help.
What are your comments and opinions?
If you have lupus, what has your experience been? What do you recommend for other patients?
Do you have any questions to ask Dr. Thomas?
Please click on “Leave a Comment” above to comment.
Please support “The Lupus Encyclopedia” blog post page
Click on “SUPPORT” at the top of the page to learn how you can support “The Lupus Encyclopedia“
No comment yet, add your voice below!
Leave a comment