Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network
Abstract Background Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods Patients from US academic medical centers with class I...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-024-03275-z |
| _version_ | 1827326598095831040 |
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| author | Peter M. Izmirly Mimi Y. Kim Philip M. Carlucci Katherine Preisinger Brooke Z. Cohen Kristina Deonaraine Devyn Zaminski Maria Dall’Era Kenneth Kalunian Andrea Fava H. Michael Belmont Ming Wu Chaim Putterman Jennifer Anolik Jennifer L. Barnas Betty Diamond Anne Davidson David Wofsy Diane Kamen Judith A. James Joel M. Guthridge William Apruzzese Deepak A. Rao Michael H. Weisman The Accelerating Medicines Partnership in RA/SLE Network Michelle Petri Jill Buyon Richard Furie |
| author_facet | Peter M. Izmirly Mimi Y. Kim Philip M. Carlucci Katherine Preisinger Brooke Z. Cohen Kristina Deonaraine Devyn Zaminski Maria Dall’Era Kenneth Kalunian Andrea Fava H. Michael Belmont Ming Wu Chaim Putterman Jennifer Anolik Jennifer L. Barnas Betty Diamond Anne Davidson David Wofsy Diane Kamen Judith A. James Joel M. Guthridge William Apruzzese Deepak A. Rao Michael H. Weisman The Accelerating Medicines Partnership in RA/SLE Network Michelle Petri Jill Buyon Richard Furie |
| author_sort | Peter M. Izmirly |
| collection | DOAJ |
| description | Abstract Background Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. Results Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93–7.33]; p = 0.069). Conclusions CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response. |
| first_indexed | 2024-03-07T14:47:55Z |
| format | Article |
| id | doaj.art-aa6c6fe2475645d1b8b302bc77c6beb6 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-07T14:47:55Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-aa6c6fe2475645d1b8b302bc77c6beb62024-03-05T19:51:52ZengBMCArthritis Research & Therapy1478-63622024-02-0126111010.1186/s13075-024-03275-zLongitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus NetworkPeter M. Izmirly0Mimi Y. Kim1Philip M. Carlucci2Katherine Preisinger3Brooke Z. Cohen4Kristina Deonaraine5Devyn Zaminski6Maria Dall’Era7Kenneth Kalunian8Andrea Fava9H. Michael Belmont10Ming Wu11Chaim Putterman12Jennifer Anolik13Jennifer L. Barnas14Betty Diamond15Anne Davidson16David Wofsy17Diane Kamen18Judith A. James19Joel M. Guthridge20William Apruzzese21Deepak A. Rao22Michael H. Weisman23The Accelerating Medicines Partnership in RA/SLE NetworkMichelle Petri24Jill Buyon25Richard Furie26New York University Grossman School of MedicineAlbert Einstein College of MedicineNew York University Grossman School of MedicineNew York University Grossman School of MedicineNew York University Grossman School of MedicineNew York University Grossman School of MedicineNew York University Grossman School of MedicineUniversity of California San FranciscoUniversity of California San DiegoJohns Hopkins UniversityNew York University Grossman School of MedicineNew York University Grossman School of MedicineAzrieli Faculty of MedicineUniversity of Rochester Medical CenterUniversity of Rochester Medical CenterZucker School of Medicine at Hofstra/NorthwellZucker School of Medicine at Hofstra/NorthwellUniversity of California San FranciscoMedical University of South CarolinaOklahoma Medical Research FoundationOklahoma Medical Research FoundationPfizer Inc.Brigham and Women’s HospitalStanford UniversityJohns Hopkins UniversityNew York University Grossman School of MedicineZucker School of Medicine at Hofstra/NorthwellAbstract Background Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR < 0.5; (2) normal serum creatinine (≤ 1.3 mg/dL) or, if abnormal, ≤ 125% of baseline; and (3) prednisone ≤ 10 mg/day. Partial response (PR) required the following: (1) > 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. Results Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93–7.33]; p = 0.069). Conclusions CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.https://doi.org/10.1186/s13075-024-03275-zLupus nephritisSystemic lupus erythematosus (SLE)OutcomeRenal biopsy |
| spellingShingle | Peter M. Izmirly Mimi Y. Kim Philip M. Carlucci Katherine Preisinger Brooke Z. Cohen Kristina Deonaraine Devyn Zaminski Maria Dall’Era Kenneth Kalunian Andrea Fava H. Michael Belmont Ming Wu Chaim Putterman Jennifer Anolik Jennifer L. Barnas Betty Diamond Anne Davidson David Wofsy Diane Kamen Judith A. James Joel M. Guthridge William Apruzzese Deepak A. Rao Michael H. Weisman The Accelerating Medicines Partnership in RA/SLE Network Michelle Petri Jill Buyon Richard Furie Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network Arthritis Research & Therapy Lupus nephritis Systemic lupus erythematosus (SLE) Outcome Renal biopsy |
| title | Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network |
| title_full | Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network |
| title_fullStr | Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network |
| title_full_unstemmed | Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network |
| title_short | Longitudinal patterns and predictors of response to standard-of-care therapy in lupus nephritis: data from the Accelerating Medicines Partnership Lupus Network |
| title_sort | longitudinal patterns and predictors of response to standard of care therapy in lupus nephritis data from the accelerating medicines partnership lupus network |
| topic | Lupus nephritis Systemic lupus erythematosus (SLE) Outcome Renal biopsy |
| url | https://doi.org/10.1186/s13075-024-03275-z |
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