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Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials
OBJECTIVES: In the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We inve...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213793/ https://www.ncbi.nlm.nih.gov/pubmed/35580976 http://dx.doi.org/10.1136/annrheumdis-2021-221847 |
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author | Bruce, Ian N Furie, Richard A Morand, Eric F Manzi, Susan Tanaka, Yoshiya Kalunian, Kenneth C. Merrill, Joan T Puzio, Patricia Maho, Emmanuelle Kleoudis, Christi Albulescu, Marius Hultquist, Micki Tummala, Raj |
author_facet | Bruce, Ian N Furie, Richard A Morand, Eric F Manzi, Susan Tanaka, Yoshiya Kalunian, Kenneth C. Merrill, Joan T Puzio, Patricia Maho, Emmanuelle Kleoudis, Christi Albulescu, Marius Hultquist, Micki Tummala, Raj |
author_sort | Bruce, Ian N |
collection | PubMed |
description | OBJECTIVES: In the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results. METHODS: TULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient. RESULTS: Most patients (78%–85%) had concordant BICLA and SRI(4) outcomes (Cohen’s Kappa 0.6–0.7, nominal p<0.001). Dual BICLA/SRI(4) response rates favoured anifrolumab over placebo in TULIP-1, TULIP-2 and MUSE (all nominal p≤0.004). A discordant TULIP-1 BICLA non-responder/SRI(4) responder subgroup was identified (40/364, 11% of TULIP-1 population), comprising more patients receiving placebo (n=28) than anifrolumab (n=12). In this subgroup, placebo-treated patients had lower baseline disease activity, joint counts and glucocorticoid tapering rates, and more placebo-treated patients had arthritis response than anifrolumab-treated patients. CONCLUSIONS: Across trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA non-responder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials. TRIAL REGISTRATION NUMBERS: NCT02446912 and NCT02446899. |
format | Online Article Text |
id | pubmed-9213793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-92137932022-07-08 Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials Bruce, Ian N Furie, Richard A Morand, Eric F Manzi, Susan Tanaka, Yoshiya Kalunian, Kenneth C. Merrill, Joan T Puzio, Patricia Maho, Emmanuelle Kleoudis, Christi Albulescu, Marius Hultquist, Micki Tummala, Raj Ann Rheum Dis Systemic Lupus Erythematosus OBJECTIVES: In the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results. METHODS: TULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient. RESULTS: Most patients (78%–85%) had concordant BICLA and SRI(4) outcomes (Cohen’s Kappa 0.6–0.7, nominal p<0.001). Dual BICLA/SRI(4) response rates favoured anifrolumab over placebo in TULIP-1, TULIP-2 and MUSE (all nominal p≤0.004). A discordant TULIP-1 BICLA non-responder/SRI(4) responder subgroup was identified (40/364, 11% of TULIP-1 population), comprising more patients receiving placebo (n=28) than anifrolumab (n=12). In this subgroup, placebo-treated patients had lower baseline disease activity, joint counts and glucocorticoid tapering rates, and more placebo-treated patients had arthritis response than anifrolumab-treated patients. CONCLUSIONS: Across trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA non-responder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials. TRIAL REGISTRATION NUMBERS: NCT02446912 and NCT02446899. BMJ Publishing Group 2022-07 2022-05-17 /pmc/articles/PMC9213793/ /pubmed/35580976 http://dx.doi.org/10.1136/annrheumdis-2021-221847 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Systemic Lupus Erythematosus Bruce, Ian N Furie, Richard A Morand, Eric F Manzi, Susan Tanaka, Yoshiya Kalunian, Kenneth C. Merrill, Joan T Puzio, Patricia Maho, Emmanuelle Kleoudis, Christi Albulescu, Marius Hultquist, Micki Tummala, Raj Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials |
title | Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials |
title_full | Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials |
title_fullStr | Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials |
title_full_unstemmed | Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials |
title_short | Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials |
title_sort | concordance and discordance in sle clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials |
topic | Systemic Lupus Erythematosus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213793/ https://www.ncbi.nlm.nih.gov/pubmed/35580976 http://dx.doi.org/10.1136/annrheumdis-2021-221847 |
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