Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS
Introduction High-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the addition of voclosporin to low-dose GCs...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2024-11-01
|
| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/11/2/e001319.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846169575506313216 |
|---|---|
| author | Kenneth Kalunian Neil Solomons Maria Dall'Era Anca D Askanase Matt Truman Ernie Yap Lucy S Hodge |
| author_facet | Kenneth Kalunian Neil Solomons Maria Dall'Era Anca D Askanase Matt Truman Ernie Yap Lucy S Hodge |
| author_sort | Kenneth Kalunian |
| collection | DOAJ |
| description | Introduction High-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the addition of voclosporin to low-dose GCs and mycophenolate mofetil (MMF) would reduce exposure to the toxicities of high-dose GC-based dual immunosuppressive therapy regimens, resulting in an improved safety profile without compromising efficacy.Methods Propensity score matching generated two groups of matched participants from the voclosporin arms (in combination with MMF (2 g/day) and low-dose GCs) of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies and the MMF (3 g/day) and intravenous cyclophosphamide (IVC) arms (both in combination with high-dose GCs) of the Aspreva Lupus Management Study (ALMS) induction study. Safety and efficacy outcomes were assessed over 6 months.Results There were 179 matched participants identified between the AURA-LV/AURORA 1 studies and ALMS. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants of ALMS; more voclosporin-treated participants reported AEs by preferred term of glomerular filtration rate decreased, hypertension and anaemia. The incidence of serious AEs was similar across treatments. There were four (2.2%) deaths in IVC- and MMF-treated participants of ALMS compared with seven (3.9%) deaths in voclosporin-treated participants. Significantly more voclosporin-treated participants achieved a ≥25% reduction in urine protein creatinine ratio (UPCR) from baseline at 3 months and ≥50% reduction in UPCR from baseline at 6 months.Conclusions Compared with the high-dose GC-based regimens used in ALMS, voclosporin-based triple immunosuppressive therapy resulted in fewer AEs overall and greater and earlier reductions in proteinuria over the first 6 months of treatment. These data reinforce the feasibility of using low doses of GCs and MMF to treat LN when combined with voclosporin as a third agent. |
| format | Article |
| id | doaj-art-d816f2ebf6dd4088bbd3aa4840138f13 |
| institution | Kabale University |
| issn | 2053-8790 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Lupus Science and Medicine |
| spelling | doaj-art-d816f2ebf6dd4088bbd3aa4840138f132024-11-12T20:45:08ZengBMJ Publishing GroupLupus Science and Medicine2053-87902024-11-0111210.1136/lupus-2024-001319Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMSKenneth Kalunian0Neil Solomons1Maria Dall'Era2Anca D Askanase3Matt Truman4Ernie Yap5Lucy S Hodge63University of California, San Diego, La Jolla, United States of AmericaAurinia Pharmaceuticals Inc, Victoria, British Columbia, CanadaUniversity of California San Francisco School of Medicine, San Francisco, California, USADepartment of Medicine, Columbia University Irving Medical Center, New York, New York, USAAurinia Pharmaceuticals Inc, Victoria, British Columbia, Canada2Dept. of Medicine, Columbia University Medical Center, New York, USAAurinia Pharmaceuticals Inc, Edmonton, Alberta, CanadaIntroduction High-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the addition of voclosporin to low-dose GCs and mycophenolate mofetil (MMF) would reduce exposure to the toxicities of high-dose GC-based dual immunosuppressive therapy regimens, resulting in an improved safety profile without compromising efficacy.Methods Propensity score matching generated two groups of matched participants from the voclosporin arms (in combination with MMF (2 g/day) and low-dose GCs) of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies and the MMF (3 g/day) and intravenous cyclophosphamide (IVC) arms (both in combination with high-dose GCs) of the Aspreva Lupus Management Study (ALMS) induction study. Safety and efficacy outcomes were assessed over 6 months.Results There were 179 matched participants identified between the AURA-LV/AURORA 1 studies and ALMS. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants of ALMS; more voclosporin-treated participants reported AEs by preferred term of glomerular filtration rate decreased, hypertension and anaemia. The incidence of serious AEs was similar across treatments. There were four (2.2%) deaths in IVC- and MMF-treated participants of ALMS compared with seven (3.9%) deaths in voclosporin-treated participants. Significantly more voclosporin-treated participants achieved a ≥25% reduction in urine protein creatinine ratio (UPCR) from baseline at 3 months and ≥50% reduction in UPCR from baseline at 6 months.Conclusions Compared with the high-dose GC-based regimens used in ALMS, voclosporin-based triple immunosuppressive therapy resulted in fewer AEs overall and greater and earlier reductions in proteinuria over the first 6 months of treatment. These data reinforce the feasibility of using low doses of GCs and MMF to treat LN when combined with voclosporin as a third agent.https://lupus.bmj.com/content/11/2/e001319.full |
| spellingShingle | Kenneth Kalunian Neil Solomons Maria Dall'Era Anca D Askanase Matt Truman Ernie Yap Lucy S Hodge Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS Lupus Science and Medicine |
| title | Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS |
| title_full | Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS |
| title_fullStr | Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS |
| title_full_unstemmed | Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS |
| title_short | Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS |
| title_sort | comparison of a voclosporin based triple immunosuppressive therapy to high dose glucocorticoid based immunosuppressive therapy a propensity analysis of the aura lv and aurora 1 studies and alms |
| url | https://lupus.bmj.com/content/11/2/e001319.full |
| work_keys_str_mv | AT kennethkalunian comparisonofavoclosporinbasedtripleimmunosuppressivetherapytohighdoseglucocorticoidbasedimmunosuppressivetherapyapropensityanalysisoftheauralvandaurora1studiesandalms AT neilsolomons comparisonofavoclosporinbasedtripleimmunosuppressivetherapytohighdoseglucocorticoidbasedimmunosuppressivetherapyapropensityanalysisoftheauralvandaurora1studiesandalms AT mariadallera comparisonofavoclosporinbasedtripleimmunosuppressivetherapytohighdoseglucocorticoidbasedimmunosuppressivetherapyapropensityanalysisoftheauralvandaurora1studiesandalms AT ancadaskanase comparisonofavoclosporinbasedtripleimmunosuppressivetherapytohighdoseglucocorticoidbasedimmunosuppressivetherapyapropensityanalysisoftheauralvandaurora1studiesandalms AT matttruman comparisonofavoclosporinbasedtripleimmunosuppressivetherapytohighdoseglucocorticoidbasedimmunosuppressivetherapyapropensityanalysisoftheauralvandaurora1studiesandalms AT ernieyap comparisonofavoclosporinbasedtripleimmunosuppressivetherapytohighdoseglucocorticoidbasedimmunosuppressivetherapyapropensityanalysisoftheauralvandaurora1studiesandalms AT lucyshodge comparisonofavoclosporinbasedtripleimmunosuppressivetherapytohighdoseglucocorticoidbasedimmunosuppressivetherapyapropensityanalysisoftheauralvandaurora1studiesandalms |