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Treatment of Lupus: Best Practices and Guidelines [January 2025]

posted in Drugs used in lupus on December 29, 2024 by

Donald Thomas, MD

Updated January 27, 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 Steroids and Consider Initially Using IV Pulse 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).

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.

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.

A big question regarding oral steroids after using IV pulse steroids is:

“How low can we go?”

A 2025 meta-analysis from the NYU Grossman School of Medicine, Department of Rheumatology showed that there was no difference in 1-year outcomes in lupus nephritis patients who received high-dose oral steroids vs low-dose oral steroids after initial pulse IV steroids. The Rituxilup Study used no oral steroids after initial high dose intravenous steroids and high remission rates of lupus nephritis. Studies show that SLE patients are more likely to go into prolonged remission (especially in those taking hydroxychloroquine) if treated with high dose pulse IV steroids. Can we give 1-3 days of IV pulse steroids at 250 – 500 mg/kg of methylprednisolone followed by no steroids? Wouldn’t that be wonderful. It would certainly be associated with significantly less side effects, like infections, compared to patients who take daily oral steroids.

I cannot wait to see another study using no oral steroids after initial IV pulse steroids!

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.

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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.

A 2025 meta-analysis from the NYU Grossman School of Medicine, Department of Rheumatology showed that there was no difference in 1-year outcomes in lupus nephritis patients who received high-dose oral steroids vs low-dose oral steroids after initial pulse IV steroids. The Rituxilup Study used no oral steroids after initial high dose intravenous steroids and high remission rates of lupus nephritis.

See the previous sections regarding using IV pulse steroids in SLE followed by low doses of oral steroids.

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)

 

Continue Immunosuppressant Therapy for 3-5 years of Treatment before Tapering in Those who Achieve a Complete Renal Response

Previously, most guidelines had recommended 3 years of treatment before tapering immunosuppressants. Interestingly, a 2025 study of patients with proliferative lupus nephritis treated between 1998 and 2023 showed that those who had been in a complete renal response (CRR, remission) for at least 4 years prior to tapering had the best chances of not flaring after tapering. The study also demonstrated that successful discontinuation of immunosuppressants was most successful in those who had a remission of their SLE in other organs as well, and in those where there was a gradual tapering rather than an abrupt stop. Patients had to have been in remission for at least one year and had had to have been on treatment for a minimum of 3 years prior to stopping immunosuppressants. 38% of patients had lupus nephritis flares, and the flares were moderate to severe in 86% of those patients. After restarting immunosuppressants, though 70% of these patients went back into remission, 3 patients progressed to end stage kidney disease, needing dialysis and renal transplantation.

My take aways: These patients were on older therapies (mycophenolate, cyclophosphamide, and azathioprine) and not newer therapies like belimumab (Benlysta). This population was predominantly white European, who typically have less severe disease than our patients of color.  Very few patients had a renal biopsy before stopping immunosuppressants. Could the 3 who went into renal failure have possibly done much better if a biopsy were done before making the decision to stop immunosuppressants? That is possible. Unfortunately, we do not have all  the clinical information on these 3 patients. Therefore, I’m worried the results may be worse in patients of color (but this is only conjecture).

In my practice, I’d include these results in my discussion with patients. I usually rebiopsy patients after 3 years and base tapering of immunosuppressants based upon the biopsy. I still think this is probably good practice: offering a rebiopsy at 3 years and base tapering off of the biopsy results. However, I’d include this study in my discussion with the patient in case the patient would prefer to await 4 years. In a patient who refuses rebiopsy, I’d recommend that we not attempt tapering until after 4 years of lupus nephritis remission, then begin a slow taper.

For patients on Benlysta, and in whom I plan on continuing Benlysta, I actually offer them the option of biopsy vs not biopsying them before mycophenolate mofetil (MMF) tapering. Rationale = there is a study from Argentina that showed that a significant proportion of patients on MMF without Benlysta had ongoing active lupus nephritis when rebiopsied, while 90% of Benlsta + MMF patients had biopsy-proven remission.  Studies also show that Benlysta reduces the loss of renal function decline over time and organ protection for the kidneys.

 

In Patients Who Fail Therapy and Near End Stage Kidney Disease, Kidney Transplantation Should be Planned ASAP, Even Before Dialysis is Needed

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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 [January 2025]:

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

11 Comments

  1. I have been on hydroxychloroquine and azathioprine for years and have cycled through also being on either Benlysta, Saphnelo, or Rituximab but my inflammation is still high (no LN though). What would you try next?

    • I’m also concurrently on IVIG for autoimmune-mediated small fiber neuropathy.

  2. Did the Rituximab not help? I’m in the same situation, currently on IVIG, hydroxy and Azathioprine and waiting for insurance approval for Rituximab. I tried Benlysta for 2 years, no help. I have neurological, skin, gastro involvement, lots of inflammation. I’m hoping the Rituxan will help. Maybe if you took them concurrently it would help? Alone they aren’t enough.

    • I also have neuro, gi, and skin involvement, as well as joints. Unfortunately the Rituximab made me feel worse (amped up my neuropathy and swelling in my feet and made my skin all over feel itchy/burny/crawly). Of note – I took Truxima (the biosimilar) instead of brand-name Rituximab, so that may have made a difference in my response.

  3. This is great information! I will pass this on to my rheumy. Thank you, Dr. Thomas!

    • Laura: thanks for commenting. I appreciate your positive feedback… makes it all worth the work

      Good luck!

      Donald Thomas, MD

  4. Good info thanks

  5. I bought this book. It is informative about SLE for patients like me . I have LN class 4.

  6. I can’t thank you enough, just getting ready to make a med switch, this information is invaluable as you are !

  7. Thank you for this information!
    I have both lupus and RA with deformity in my fingers and toes. I’m on plaquenil, Imuran and waiting to be approved for Riximyo as the insurance declined benlysta… what are thoughts on riximyo?

    • Pilar: Riximio (a biosimilar for rituximab, Rituxan) works very well in a large number of both RA and SLE patients.
      However, since the epidemic, I leave it as one of my last drug choices.
      Reason being: Infections are the number two cause of death in SLE patients. Rituximab greatly decreases vaccine response rates. During the COVID epidemic, rituximab patients fared the worse. Last year one of my rituximab patients died of COVID, even though it was one of the “milder” strains.

      Per the 2023 EULAR guidelines, I often offer anifrolumab and belimumab next to patients. They are less likely to cause infections compared to other immunosuppressants (like Imuran) and rituximab. I have some rhupus patients who are doing very well on them (to include patients on HCQ + Imuran + anifrolumab/belimumab).

      Abatacept is another option (works best in SLE patients who have inflammatory arthritis as their major problem).

      JAK inhibitors (Xeljanz, Rinvoq, Olumiant) have also worked very well in my patients (but I avoid them in people at risk for blood clots/strokes/heart attacks/cancer)

      Methotrexate and mycophenolate can work very well.

      Since your rheumatologist chose rituximab, there must be other clinical reasons on why this was chosen, so best to ask them. Bottom line is that most patients do very well on it.

      Good luck!

      Donald Thomas, MD


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