Introduction
Lupus nephritis (LN) is a serious kidney problem that can happen in people with systemic lupus erythematosus (SLE). It occurs when the immune system mistakenly attacks the kidneys, causing inflammation and making it harder for the kidneys to filter waste. If not managed properly, about 1 in 5 people with LN can develop end-stage kidney disease within 10 years of diagnosis. LN is more common in women, which makes finding effective treatments really important. 1
Researchers have studied a range of treatments for LN. Traditional options include immunosuppressants like mycophenolate mofetil (MMF) and cyclophosphamide, which help calm the overactive immune system. In recent years, newer biologic medicines such as belimumab and voclosporin have also been developed to help manage the condition. Together, these treatments aim to reduce kidney inflammation and protect long-term kidney function.1
What is Lupkynis (Voclosporin)?
Voclosporin is a strong medicine that helps calm the immune system. It is mainly used to treat people with systemic lupus erythematosus and acute lupus nephritis, conditions where the immune system mistakenly attacks the body.2
Voclosporin is a close relative of cyclosporine, a drug first found in a type of fungus. Both work by blocking T cell activation, which reduces immune system overactivity and helps prevent cell damage caused by the immune response. Voclosporin is slightly different from cyclosporine by just one amino acid, making it more selective and a bit more powerful. Unlike cyclosporine, voclosporin was specifically developed to treat autoimmune diseases rather than for preventing organ transplant rejection. 2
Standard of Care: MMF and corticosteroids
For people with active severe lupus nephritis (LN), the current standard treatment often combines MMF and corticosteroids. MMF (mycophenolate mofetil) works by slowing down certain immune cells—B and T lymphocytes—so they don’t multiply as much. This helps control the overactive immune response that can damage the kidneys. Studies, like the Aspreva Lupus Management Study, have shown that MMF is a reliable option as an initial treatment for LN. 3
Corticosteroids are added to boost the effect, helping to reduce inflammation quickly. Together, MMF and corticosteroids form one of the main “go-to” treatment plans for managing severe lupus affecting the kidneys. Other drugs, like CNIs such as tacrolimus, can also be used because they calm the immune system and help the kidneys recover faster, but the MMF-steroid combination remains a widely used standard-of-care approach.3
Rationale for Combination
Combining Lupkynis (voclosporin) with standard-of-care treatments like mycophenolate mofetil (MMF) and low-dose steroids makes a big difference for people with lupus nephritis. It increases the chance of achieving complete kidney response after a year compared to those on MMF and steroids alone. Importantly, adding voclosporin didn’t bring extra safety concerns. Serious side effects, including infections, were similar in both groups. This combination approach is a major step forward in helping patients manage active lupus nephritis more effectively. 4
Clinical Trial Evidence
As per the AURORA 1 study, patients taking voclosporin alongside MMF and steroids had a much higher chance of achieving complete kidney response after a year compared to those on MMF and steroids alone, 41% versus 23%.4
In the AURORA 2 study, patients taking Lupkynis along with SOC maintained better kidney function and experienced greater reductions in protein in the urine compared to those on SOC alone. At 36 months, about 51% of patients on Lupkynis reached complete renal response, compared with 39% in the control group, and 74% achieved partial renal response versus 69% in the control group. Overall, more patients on Lupkynis had a good renal outcome, meaning their kidney function stayed stable without flares. 5
Plus, Lupkynis allowed patients to maintain lower steroid doses while supporting kidney health, which can help reduce the long-term risks associated with steroid use. This evidence shows that adding Lupkynis to SOC provides a meaningful improvement in kidney outcomes for lupus nephritis patients.5
Safety Profile
Voclosporin, when used in combination therapy, is generally effective but requires careful monitoring by doctors experienced in managing lupus nephritis and calcineurin inhibitor complications. Common side effects include nausea, diarrhea, stomach discomfort, dizziness, and tingling sensations. The drug can also affect kidney function and blood pressure, sometimes requiring dose adjustments in up to half of patients. Less common but more serious risks include severe infections, certain cancers, heart rhythm changes, high potassium levels, and nerve-related issues.2
In the AURORA 2 study, most patients experienced side effects (86.2% in the voclosporin group vs. 80% in the control group), but the majority were mild or moderate in severity. Serious side effects were similar between groups (18.1% vs. 23%), and the frequency of side effects decreased each year. Fewer patients stopped treatment due to side effects in the voclosporin group (9.5%) compared with the control group (17%).5
In terms of liver safety, studies show that voclosporin may cause small, temporary increases in liver enzymes in a few patients, but these changes are usually mild and similar to those seen with conventional therapy. 2
Limitations: Patient selection and monitoring challenges
Voclosporin can be an effective treatment for certain patients, but there are important limits and monitoring needs to keep in mind. Some patients shouldn’t use it at all, such as those with a known serious allergy to Lupkynis or its ingredients, or those taking strong CYP3A4 inhibitors like ketoconazole, itraconazole, or clarithromycin. 6
Even in suitable patients, careful monitoring is essential. Lupkynis can affect the kidneys, blood pressure, nerves, and heart, so doctors often check kidney function, blood pressure, neurological health, potassium levels, and heart rhythm. Live vaccines should be avoided, and in rare cases, it can affect red blood cells, meaning treatment may need to be adjusted or stopped. These precautions ensure that patients get the benefits of Lupkynis while minimizing risks.6
Future Perspectives
Researchers are exploring new ways to make treatments even better. Voclosporin is being studied to see how it compares long-term with other drugs like low-dose cyclosporin or tacrolimus. Experts are also looking at how it can be used safely in combination with other therapies, the best timing to start treatment, and which patients benefit the most.7
There are still questions to answer, such as the effects of low-dose voclosporin in people with reduced kidney function and the exact kidney function limits for safe use. Ongoing studies aim to fill these gaps, expand treatment options, and help doctors personalize therapy for patients. 7
Conclusion
Lupkynis (voclosporin), when combined with standard therapies like MMF and low-dose steroids, has shown meaningful improvements in kidney function and overall outcomes for patients with active lupus nephritis. Clinical studies demonstrate that it helps more patients achieve complete or partial kidney responses while allowing lower steroid use, and it is generally well tolerated.
Note:
This content is for educational purposes only and is not a substitute for professional medical advice. Always consult your doctor or healthcare provider before starting, stopping, or changing any treatment.
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References:
- Patel JP, Hardaswani D, Chaniyara SR, et al. Navigating Lupus Nephritis: A Comprehensive Review of the Current Treatment Trends. Cureus. 2024;16(10):e72644. Published 2024 Oct 29. doi:10.7759/cureus.72644
- LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Voclosporin. [Updated 2021 Aug 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK574095/
- An Y, Zhang H, Liu Z. Individualizing Therapy in Lupus Nephritis. Kidney Int Rep. 2019;4(10):1366-1372. Published 2019 Aug 20. doi:10.1016/j.ekir.2019.08.005
- Rovin BH, van Vollenhoven R, Felten R, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021;397(10289):2070-2080.
- Saxena A, Ginzler EM, Gibson K, Satirapoj B, Zuta Santillán AE, Levchenko O, Navarra S, Atsumi T, Yasuda S, et al. Safety and efficacy of long-term voclosporin treatment for lupus nephritis in the phase 3 AURORA 2 clinical trial. Arthritis Rheumatol. 2023;75:doi:10.1002/art.42657.
- LUPKYNISTM Prescribing Information
- Ashinze P, Mafua N, Banerjee S, et al. Voclosporin: A comprehensive review of its role as a novel calcineurin inhibitor in the management of systemic lupus erythematosus. Medicine (Baltimore). 2025;104(25):e42858. doi:10.1097/MD.0000000000042858
