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Murray B Urowitz - One of the best experts on this subject based on the ideXlab platform.

  • identifying a response for the systemic lupus erythematosus disease activity glucocorticoid index SLEDAI 2kg
    Arthritis Care and Research, 2021
    Co-Authors: Zahi Touma, Dafna D Gladman, Moe Zandy, Nicole Anderson, Murray B Urowitz
    Abstract:

    OBJECTIVE To compare the performance of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K Glucocorticoids (SLEDAI-2KG) indices in identifying responders to standard of care therapy. METHODS Data from adult patients seen between 1995 and 2018 at the University of Toronto Lupus Clinic were analyzed. Patients with active disease (SLEDAI-2K score ≥6) and receiving prednisone ≥5 mg/day, and with a follow-up visit at 9 months, were studied. Response to standard of care therapy at first follow-up visit was assessed using the SLEDAI-2K and SLEDAI-2KG. The performances of the SLEDAI-2K and SLEDAI-2KG were compared using a cutoff point of 4. RESULTS In a cohort of 188, the majority of patients were female (86.0%) and White (47.9%). Of 188 patients, 145 (77.1%) were responders and had a decrease in SLEDAI-2K score of ≥4. The SLEDAI-2KG identified 142 (97.9%) responders among the SLEDAI-2K responders. More importantly, the SLEDAI-2KG identified 11 (25.6%) additional responders among SLEDAI-2K nonresponders (n = 43). This resulted from the ability of the SLEDAI-2KG to account for the decrease in glucocorticoids dose. CONCLUSION The SLEDAI-2KG provides a novel concept for the assessment of lupus disease activity while accounting for glucocorticoids dosage to reflect on disease activity overall at a particular visit. The SLEDAI-2KG accounts for the disease activity for each descriptor while also accounting for the current glucocorticoids dosage. The SLEDAI-2KG adds 1 additional variable (glucocorticoids dosage) to the SLEDAI-2K, which could alter response rates in drug trials and observational studies.

  • 10 performance of SLEDAI 2k responder index 50 in a randomized placebo controlled trial with ustekinumab ust in systemic lupus erythematosus
    Lupus science & medicine, 2019
    Co-Authors: Zahi Touma, Dafna D Gladman, Shawn Rose, R Gordon, K Fei, Irene Y Gregan, Murray B Urowitz
    Abstract:

    Background While traditional Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) scoring assesses complete SLE response for individual disease manifestations, the SLEDAI-2K Responder Index-50 (S2K RI-50) evaluates responses using partial improvement (50%) in each of the 9 organ-systems of SLEDAI-2K and generates a total score. We aimed to evaluate the performance of S2K RI-50 at 24 weeks in a randomized, placebo (PBO) controlled trial of UST in patients with moderate-to-severe SLE disease activity to ascertain a minimal threshold of partial improvement. Methods The UST phase 2, PBO-controlled study enrolled adults with active disease (SLEDAI score 6 with 1 BILAG A and /or 2 BILAG B scores) despite standard-of-care therapy. Patients (n=102) were randomized (3:2) to receive UST IV~6 mg/kg or PBO at week (wk) 0, followed by SC injections of UST 90 mg q8w or PBO beginning at wk8, both added to standard of care. We calculated S2K RI-50 response in patients receiving UST (n=62) vs PBO (n=40) at wk24 using increasing S2K RI-50 reductions of 1, 2, 3, 4, 5, or 6 points from baseline to determine 50% improvement. In order to determine a minimal cut-off to discriminate a treatment effect reflecting partial improvement, nominal level was set at 0.05 for this post hoc analysis. Results The performance of S2K RI-50 in detecting the treatment difference between UST and PBO with various cut-offs is presented in table 1. A 2-point reduction in S2K RI-50 was the lowest threshold to demonstrate a p-value Conclusions S2K RI-50 captures partial improvement of 50% in SLE disease activity in the most common disease manifestations in SLE. S2K RI-50 could be used as an outcome in clinical trials as a clinically meaningful measure of partial improvement. Funding Source(s): Jannsen Research and Development, LLC, supported this study.

  • a novel lupus activity index accounting for glucocorticoids SLEDAI 2k glucocorticoid index
    Rheumatology, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, Nicole Anderson, Murray B Urowitz
    Abstract:

    Objective To develop and validate a modification of SLEDAI-2K to accurately describe disease activity while accounting for glucocorticoid (GC) doses. Methods The first two phases focused on the development of the index. Phase 1: identification of scenarios of real patients seen prospectively in a longitudinal cohort. Phase 2: derivation of an equation that explains the association between SLEDAI-2K and GC doses using physician global assessment as the external construct. Phase 3: comparison of SLEDAI-2K and SLEDAI-2K GC (SLEDAI-2KG), using different cut-off points (4-7), in identifying responders in response to therapy. Results In phase 1, 150 scenarios with different organ involvement and a range of GC doses were identified. In phase 2, three rheumatologists ranked disease activity using physician global assessment. A quadratic linear regression model relating GC doses and SLEDAI-2K resulted in the following equation: SLEDAI-2KG score = SLEDAI-2K score + [0.32 × GC - 0.0031 × GC2]. The weighted score of different GC doses was derived. In phase 3, SLEDAI-2KG identified more responders in a total of 111 patients at 6 months (84 vs 93%) and at 12 months (76 vs 92%) compared with SLEDAI-2K. SLEDAI-2KG performances were superior to SLEDAI-2K with all cut-off points (5-7). Conclusion We developed a modification of SLEDAI-2K, SLEDAI-2KG, that describes disease activity while accounting for GC dose category. SLEDAI-2KG identifies more responders compared with SLEDAI-2K.

  • fri0395 sle disease activity index glucocorticoid index SLEDAI 2kg identifies more responders than SLEDAI 2k
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, N M Anderson, Murray B Urowitz
    Abstract:

    Background Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) is one of the most commonly used disease activity indices in clinical practice and research but this index doesn’t account for severity within each descriptor. Moreover, in clinical trials, the use of standard of care (SoC), which includes glucocorticoid (GC) often confounds trial results. We developed and validated a novel lupus disease activity index, SLEDAI-2K GC (SLEDAI-2KG), that describes disease activity while accounting for GC dose. SLEDAI-2KG has the same descriptors as SLEDAI-2K in addition to a new descriptor “GC” with different weight scores based on the dose of GC. Furthermore, SLEDAI-2KG has a low administration burden and a simple scoring system similar to SLEDAI-2K. Objectives We aimed to compare the performance of SLEDAI-2K and SGI in identifying responders in response to SoC. Methods Patients have been followed prospectively according to a standard protocol between January 2011 and January 2014, at a single lupus centre, with active disease (SLEDAI-2K≥6), on prednisone ≥10 mg/day, and with follow up visits within 5–24 months were studied. Treatment was determined based on the judgment of the treating rheumatologist. Response to SoC therapy, at first follow up visit, was assessed by SLEDAI- 2K and SLEDAI-2KG. Responders were defined based on the decrease in SLEDAI-2K and SGI score by ≥4. The performance of SLEDAI-2K and SGI was also compared using different cut-off points; 5, 6 and 7. Descriptive analysis was used. Results 111 patients met the inclusion criteria of the study and were further analysed. Patients’ characteristics are represented in table 1. SLEDAI-2KG identified more responders at 6 months (94% vs. 84%) and at 12 months (92% vs. 76%) compared to SLEDAI-2K by cut off of 4. SLEDAI-2KG also identified more responders with cut off points 5, 6 and 7 (table 2). Conclusions The novel index, SLEDAI-2KG, is superior to SLEDAI-2K in identifying responders at 6 and 12 months accounting for steroid dose and thus adjusting for severity within each descriptor of SLEDAI-2K. SLEDAI-2KG has the ability to enhance analyses in clinical trials to differentiate between responders on minimal and moderate/large doses of GC. Disclosure of Interest Z. Touma Grant/research support from: GlaxoSmithKline, D. Gladman: None declared, J. Su: None declared, N. Anderson: None declared, M. Urowitz Grant/research support from: GlaxoSmithKline

  • fri0339 SLEDAI 2k responder index 50 is effective in demonstrating partial response in a phase 2 randomised placebo controlled study of ustekinumab in patients with active systemic lupus erythematosus
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, Murray B Urowitz, Marc Chevrier, Carrie Wagner, B Hsu, Shawn Rose, B Zhou, R Gordon
    Abstract:

    Background Ustekinumab (UST), a monoclonal antibody that targets shared p40 subunit of cytokines IL-12 and IL-23, is being investigated in pts w/active systemic lupus erythematosus(SLE). While traditional SLE Disease Activity Index 2000(SLEDAI-2K)scoring assesses complete SLE response for individual disease manifestations, SLEDAI-2K Responder Index-50(S2K RI-50)can be used to evaluate SLE responses using partial improvement(≥50%)in each domain. Objectives To evaluate SLEDAI-2K vs S2K RI-50 response in a randomised, PBO-controlled trial of UST in pts w/active SLE. Methods We conducted a Ph2, PBO-controlled study in adults w/active disease(SLEDAI score ≥6 w/≥1 BILAG A and /or ≥2 BILAG B scores)despite standard-of-care therapy. Pts(n=102)were randomised(3:2) to UST IV~6 mg/kg or PBO at wk0, followed by SC inj of UST 90 mg q8w or PBO beginning at wk8, both added to standard-of-care. We calculated S2K RI-50 response at wk24 using various thresholds to define response including decrease of at least 1,2,3,4,5, or6 points from baseline(BL) in S2K RI-50 score. We also compared proportion of pts w/SLEDAI-2K response vs S2K RI-50 response in pts receiving UST(n=62)vs PBO(n=40)at wk24. Results Change from BL SLEDAI-2K and S2K RI-50 scores were strongly correlated(R=0.89,p Conclusions S2K RI-50 is an instrument that can capture partial clinically important improvement of ≥50% in SLE disease manifestations. The data suggests cutpoints for defining S2K RI-50 response in clinical trials of pts w/moderate-severe SLE disease activity. Disclosure of Interest Z. Touma Grant/research support from: Janssen Research and Development, LLC, M. Urowitz Grant/research support from: Janssen Research and Development, LLC, D. Gladman Grant/research support from: Janssen Research and Development, LLC, C. Wagner Employee of: Janssen Research and Development, LLC, B. Hsu Employee of: Janssen Research and Development, LLC, M. Chevrier Employee of: Janssen Research and Development, LLC, S. Rose Employee of: Janssen Research and Development, LLC, B. Zhou Employee of: Janssen Research and Development, LLC, R. Gordon Employee of: Janssen Research and Development, LLC

Dafna D Gladman - One of the best experts on this subject based on the ideXlab platform.

  • identifying a response for the systemic lupus erythematosus disease activity glucocorticoid index SLEDAI 2kg
    Arthritis Care and Research, 2021
    Co-Authors: Zahi Touma, Dafna D Gladman, Moe Zandy, Nicole Anderson, Murray B Urowitz
    Abstract:

    OBJECTIVE To compare the performance of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K Glucocorticoids (SLEDAI-2KG) indices in identifying responders to standard of care therapy. METHODS Data from adult patients seen between 1995 and 2018 at the University of Toronto Lupus Clinic were analyzed. Patients with active disease (SLEDAI-2K score ≥6) and receiving prednisone ≥5 mg/day, and with a follow-up visit at 9 months, were studied. Response to standard of care therapy at first follow-up visit was assessed using the SLEDAI-2K and SLEDAI-2KG. The performances of the SLEDAI-2K and SLEDAI-2KG were compared using a cutoff point of 4. RESULTS In a cohort of 188, the majority of patients were female (86.0%) and White (47.9%). Of 188 patients, 145 (77.1%) were responders and had a decrease in SLEDAI-2K score of ≥4. The SLEDAI-2KG identified 142 (97.9%) responders among the SLEDAI-2K responders. More importantly, the SLEDAI-2KG identified 11 (25.6%) additional responders among SLEDAI-2K nonresponders (n = 43). This resulted from the ability of the SLEDAI-2KG to account for the decrease in glucocorticoids dose. CONCLUSION The SLEDAI-2KG provides a novel concept for the assessment of lupus disease activity while accounting for glucocorticoids dosage to reflect on disease activity overall at a particular visit. The SLEDAI-2KG accounts for the disease activity for each descriptor while also accounting for the current glucocorticoids dosage. The SLEDAI-2KG adds 1 additional variable (glucocorticoids dosage) to the SLEDAI-2K, which could alter response rates in drug trials and observational studies.

  • 10 performance of SLEDAI 2k responder index 50 in a randomized placebo controlled trial with ustekinumab ust in systemic lupus erythematosus
    Lupus science & medicine, 2019
    Co-Authors: Zahi Touma, Dafna D Gladman, Shawn Rose, R Gordon, K Fei, Irene Y Gregan, Murray B Urowitz
    Abstract:

    Background While traditional Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) scoring assesses complete SLE response for individual disease manifestations, the SLEDAI-2K Responder Index-50 (S2K RI-50) evaluates responses using partial improvement (50%) in each of the 9 organ-systems of SLEDAI-2K and generates a total score. We aimed to evaluate the performance of S2K RI-50 at 24 weeks in a randomized, placebo (PBO) controlled trial of UST in patients with moderate-to-severe SLE disease activity to ascertain a minimal threshold of partial improvement. Methods The UST phase 2, PBO-controlled study enrolled adults with active disease (SLEDAI score 6 with 1 BILAG A and /or 2 BILAG B scores) despite standard-of-care therapy. Patients (n=102) were randomized (3:2) to receive UST IV~6 mg/kg or PBO at week (wk) 0, followed by SC injections of UST 90 mg q8w or PBO beginning at wk8, both added to standard of care. We calculated S2K RI-50 response in patients receiving UST (n=62) vs PBO (n=40) at wk24 using increasing S2K RI-50 reductions of 1, 2, 3, 4, 5, or 6 points from baseline to determine 50% improvement. In order to determine a minimal cut-off to discriminate a treatment effect reflecting partial improvement, nominal level was set at 0.05 for this post hoc analysis. Results The performance of S2K RI-50 in detecting the treatment difference between UST and PBO with various cut-offs is presented in table 1. A 2-point reduction in S2K RI-50 was the lowest threshold to demonstrate a p-value Conclusions S2K RI-50 captures partial improvement of 50% in SLE disease activity in the most common disease manifestations in SLE. S2K RI-50 could be used as an outcome in clinical trials as a clinically meaningful measure of partial improvement. Funding Source(s): Jannsen Research and Development, LLC, supported this study.

  • a novel lupus activity index accounting for glucocorticoids SLEDAI 2k glucocorticoid index
    Rheumatology, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, Nicole Anderson, Murray B Urowitz
    Abstract:

    Objective To develop and validate a modification of SLEDAI-2K to accurately describe disease activity while accounting for glucocorticoid (GC) doses. Methods The first two phases focused on the development of the index. Phase 1: identification of scenarios of real patients seen prospectively in a longitudinal cohort. Phase 2: derivation of an equation that explains the association between SLEDAI-2K and GC doses using physician global assessment as the external construct. Phase 3: comparison of SLEDAI-2K and SLEDAI-2K GC (SLEDAI-2KG), using different cut-off points (4-7), in identifying responders in response to therapy. Results In phase 1, 150 scenarios with different organ involvement and a range of GC doses were identified. In phase 2, three rheumatologists ranked disease activity using physician global assessment. A quadratic linear regression model relating GC doses and SLEDAI-2K resulted in the following equation: SLEDAI-2KG score = SLEDAI-2K score + [0.32 × GC - 0.0031 × GC2]. The weighted score of different GC doses was derived. In phase 3, SLEDAI-2KG identified more responders in a total of 111 patients at 6 months (84 vs 93%) and at 12 months (76 vs 92%) compared with SLEDAI-2K. SLEDAI-2KG performances were superior to SLEDAI-2K with all cut-off points (5-7). Conclusion We developed a modification of SLEDAI-2K, SLEDAI-2KG, that describes disease activity while accounting for GC dose category. SLEDAI-2KG identifies more responders compared with SLEDAI-2K.

  • fri0395 sle disease activity index glucocorticoid index SLEDAI 2kg identifies more responders than SLEDAI 2k
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, N M Anderson, Murray B Urowitz
    Abstract:

    Background Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) is one of the most commonly used disease activity indices in clinical practice and research but this index doesn’t account for severity within each descriptor. Moreover, in clinical trials, the use of standard of care (SoC), which includes glucocorticoid (GC) often confounds trial results. We developed and validated a novel lupus disease activity index, SLEDAI-2K GC (SLEDAI-2KG), that describes disease activity while accounting for GC dose. SLEDAI-2KG has the same descriptors as SLEDAI-2K in addition to a new descriptor “GC” with different weight scores based on the dose of GC. Furthermore, SLEDAI-2KG has a low administration burden and a simple scoring system similar to SLEDAI-2K. Objectives We aimed to compare the performance of SLEDAI-2K and SGI in identifying responders in response to SoC. Methods Patients have been followed prospectively according to a standard protocol between January 2011 and January 2014, at a single lupus centre, with active disease (SLEDAI-2K≥6), on prednisone ≥10 mg/day, and with follow up visits within 5–24 months were studied. Treatment was determined based on the judgment of the treating rheumatologist. Response to SoC therapy, at first follow up visit, was assessed by SLEDAI- 2K and SLEDAI-2KG. Responders were defined based on the decrease in SLEDAI-2K and SGI score by ≥4. The performance of SLEDAI-2K and SGI was also compared using different cut-off points; 5, 6 and 7. Descriptive analysis was used. Results 111 patients met the inclusion criteria of the study and were further analysed. Patients’ characteristics are represented in table 1. SLEDAI-2KG identified more responders at 6 months (94% vs. 84%) and at 12 months (92% vs. 76%) compared to SLEDAI-2K by cut off of 4. SLEDAI-2KG also identified more responders with cut off points 5, 6 and 7 (table 2). Conclusions The novel index, SLEDAI-2KG, is superior to SLEDAI-2K in identifying responders at 6 and 12 months accounting for steroid dose and thus adjusting for severity within each descriptor of SLEDAI-2K. SLEDAI-2KG has the ability to enhance analyses in clinical trials to differentiate between responders on minimal and moderate/large doses of GC. Disclosure of Interest Z. Touma Grant/research support from: GlaxoSmithKline, D. Gladman: None declared, J. Su: None declared, N. Anderson: None declared, M. Urowitz Grant/research support from: GlaxoSmithKline

  • fri0339 SLEDAI 2k responder index 50 is effective in demonstrating partial response in a phase 2 randomised placebo controlled study of ustekinumab in patients with active systemic lupus erythematosus
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, Murray B Urowitz, Marc Chevrier, Carrie Wagner, B Hsu, Shawn Rose, B Zhou, R Gordon
    Abstract:

    Background Ustekinumab (UST), a monoclonal antibody that targets shared p40 subunit of cytokines IL-12 and IL-23, is being investigated in pts w/active systemic lupus erythematosus(SLE). While traditional SLE Disease Activity Index 2000(SLEDAI-2K)scoring assesses complete SLE response for individual disease manifestations, SLEDAI-2K Responder Index-50(S2K RI-50)can be used to evaluate SLE responses using partial improvement(≥50%)in each domain. Objectives To evaluate SLEDAI-2K vs S2K RI-50 response in a randomised, PBO-controlled trial of UST in pts w/active SLE. Methods We conducted a Ph2, PBO-controlled study in adults w/active disease(SLEDAI score ≥6 w/≥1 BILAG A and /or ≥2 BILAG B scores)despite standard-of-care therapy. Pts(n=102)were randomised(3:2) to UST IV~6 mg/kg or PBO at wk0, followed by SC inj of UST 90 mg q8w or PBO beginning at wk8, both added to standard-of-care. We calculated S2K RI-50 response at wk24 using various thresholds to define response including decrease of at least 1,2,3,4,5, or6 points from baseline(BL) in S2K RI-50 score. We also compared proportion of pts w/SLEDAI-2K response vs S2K RI-50 response in pts receiving UST(n=62)vs PBO(n=40)at wk24. Results Change from BL SLEDAI-2K and S2K RI-50 scores were strongly correlated(R=0.89,p Conclusions S2K RI-50 is an instrument that can capture partial clinically important improvement of ≥50% in SLE disease manifestations. The data suggests cutpoints for defining S2K RI-50 response in clinical trials of pts w/moderate-severe SLE disease activity. Disclosure of Interest Z. Touma Grant/research support from: Janssen Research and Development, LLC, M. Urowitz Grant/research support from: Janssen Research and Development, LLC, D. Gladman Grant/research support from: Janssen Research and Development, LLC, C. Wagner Employee of: Janssen Research and Development, LLC, B. Hsu Employee of: Janssen Research and Development, LLC, M. Chevrier Employee of: Janssen Research and Development, LLC, S. Rose Employee of: Janssen Research and Development, LLC, B. Zhou Employee of: Janssen Research and Development, LLC, R. Gordon Employee of: Janssen Research and Development, LLC

Zahi Touma - One of the best experts on this subject based on the ideXlab platform.

  • identifying a response for the systemic lupus erythematosus disease activity glucocorticoid index SLEDAI 2kg
    Arthritis Care and Research, 2021
    Co-Authors: Zahi Touma, Dafna D Gladman, Moe Zandy, Nicole Anderson, Murray B Urowitz
    Abstract:

    OBJECTIVE To compare the performance of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K Glucocorticoids (SLEDAI-2KG) indices in identifying responders to standard of care therapy. METHODS Data from adult patients seen between 1995 and 2018 at the University of Toronto Lupus Clinic were analyzed. Patients with active disease (SLEDAI-2K score ≥6) and receiving prednisone ≥5 mg/day, and with a follow-up visit at 9 months, were studied. Response to standard of care therapy at first follow-up visit was assessed using the SLEDAI-2K and SLEDAI-2KG. The performances of the SLEDAI-2K and SLEDAI-2KG were compared using a cutoff point of 4. RESULTS In a cohort of 188, the majority of patients were female (86.0%) and White (47.9%). Of 188 patients, 145 (77.1%) were responders and had a decrease in SLEDAI-2K score of ≥4. The SLEDAI-2KG identified 142 (97.9%) responders among the SLEDAI-2K responders. More importantly, the SLEDAI-2KG identified 11 (25.6%) additional responders among SLEDAI-2K nonresponders (n = 43). This resulted from the ability of the SLEDAI-2KG to account for the decrease in glucocorticoids dose. CONCLUSION The SLEDAI-2KG provides a novel concept for the assessment of lupus disease activity while accounting for glucocorticoids dosage to reflect on disease activity overall at a particular visit. The SLEDAI-2KG accounts for the disease activity for each descriptor while also accounting for the current glucocorticoids dosage. The SLEDAI-2KG adds 1 additional variable (glucocorticoids dosage) to the SLEDAI-2K, which could alter response rates in drug trials and observational studies.

  • 10 performance of SLEDAI 2k responder index 50 in a randomized placebo controlled trial with ustekinumab ust in systemic lupus erythematosus
    Lupus science & medicine, 2019
    Co-Authors: Zahi Touma, Dafna D Gladman, Shawn Rose, R Gordon, K Fei, Irene Y Gregan, Murray B Urowitz
    Abstract:

    Background While traditional Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) scoring assesses complete SLE response for individual disease manifestations, the SLEDAI-2K Responder Index-50 (S2K RI-50) evaluates responses using partial improvement (50%) in each of the 9 organ-systems of SLEDAI-2K and generates a total score. We aimed to evaluate the performance of S2K RI-50 at 24 weeks in a randomized, placebo (PBO) controlled trial of UST in patients with moderate-to-severe SLE disease activity to ascertain a minimal threshold of partial improvement. Methods The UST phase 2, PBO-controlled study enrolled adults with active disease (SLEDAI score 6 with 1 BILAG A and /or 2 BILAG B scores) despite standard-of-care therapy. Patients (n=102) were randomized (3:2) to receive UST IV~6 mg/kg or PBO at week (wk) 0, followed by SC injections of UST 90 mg q8w or PBO beginning at wk8, both added to standard of care. We calculated S2K RI-50 response in patients receiving UST (n=62) vs PBO (n=40) at wk24 using increasing S2K RI-50 reductions of 1, 2, 3, 4, 5, or 6 points from baseline to determine 50% improvement. In order to determine a minimal cut-off to discriminate a treatment effect reflecting partial improvement, nominal level was set at 0.05 for this post hoc analysis. Results The performance of S2K RI-50 in detecting the treatment difference between UST and PBO with various cut-offs is presented in table 1. A 2-point reduction in S2K RI-50 was the lowest threshold to demonstrate a p-value Conclusions S2K RI-50 captures partial improvement of 50% in SLE disease activity in the most common disease manifestations in SLE. S2K RI-50 could be used as an outcome in clinical trials as a clinically meaningful measure of partial improvement. Funding Source(s): Jannsen Research and Development, LLC, supported this study.

  • a novel lupus activity index accounting for glucocorticoids SLEDAI 2k glucocorticoid index
    Rheumatology, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, Nicole Anderson, Murray B Urowitz
    Abstract:

    Objective To develop and validate a modification of SLEDAI-2K to accurately describe disease activity while accounting for glucocorticoid (GC) doses. Methods The first two phases focused on the development of the index. Phase 1: identification of scenarios of real patients seen prospectively in a longitudinal cohort. Phase 2: derivation of an equation that explains the association between SLEDAI-2K and GC doses using physician global assessment as the external construct. Phase 3: comparison of SLEDAI-2K and SLEDAI-2K GC (SLEDAI-2KG), using different cut-off points (4-7), in identifying responders in response to therapy. Results In phase 1, 150 scenarios with different organ involvement and a range of GC doses were identified. In phase 2, three rheumatologists ranked disease activity using physician global assessment. A quadratic linear regression model relating GC doses and SLEDAI-2K resulted in the following equation: SLEDAI-2KG score = SLEDAI-2K score + [0.32 × GC - 0.0031 × GC2]. The weighted score of different GC doses was derived. In phase 3, SLEDAI-2KG identified more responders in a total of 111 patients at 6 months (84 vs 93%) and at 12 months (76 vs 92%) compared with SLEDAI-2K. SLEDAI-2KG performances were superior to SLEDAI-2K with all cut-off points (5-7). Conclusion We developed a modification of SLEDAI-2K, SLEDAI-2KG, that describes disease activity while accounting for GC dose category. SLEDAI-2KG identifies more responders compared with SLEDAI-2K.

  • fri0395 sle disease activity index glucocorticoid index SLEDAI 2kg identifies more responders than SLEDAI 2k
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, N M Anderson, Murray B Urowitz
    Abstract:

    Background Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) is one of the most commonly used disease activity indices in clinical practice and research but this index doesn’t account for severity within each descriptor. Moreover, in clinical trials, the use of standard of care (SoC), which includes glucocorticoid (GC) often confounds trial results. We developed and validated a novel lupus disease activity index, SLEDAI-2K GC (SLEDAI-2KG), that describes disease activity while accounting for GC dose. SLEDAI-2KG has the same descriptors as SLEDAI-2K in addition to a new descriptor “GC” with different weight scores based on the dose of GC. Furthermore, SLEDAI-2KG has a low administration burden and a simple scoring system similar to SLEDAI-2K. Objectives We aimed to compare the performance of SLEDAI-2K and SGI in identifying responders in response to SoC. Methods Patients have been followed prospectively according to a standard protocol between January 2011 and January 2014, at a single lupus centre, with active disease (SLEDAI-2K≥6), on prednisone ≥10 mg/day, and with follow up visits within 5–24 months were studied. Treatment was determined based on the judgment of the treating rheumatologist. Response to SoC therapy, at first follow up visit, was assessed by SLEDAI- 2K and SLEDAI-2KG. Responders were defined based on the decrease in SLEDAI-2K and SGI score by ≥4. The performance of SLEDAI-2K and SGI was also compared using different cut-off points; 5, 6 and 7. Descriptive analysis was used. Results 111 patients met the inclusion criteria of the study and were further analysed. Patients’ characteristics are represented in table 1. SLEDAI-2KG identified more responders at 6 months (94% vs. 84%) and at 12 months (92% vs. 76%) compared to SLEDAI-2K by cut off of 4. SLEDAI-2KG also identified more responders with cut off points 5, 6 and 7 (table 2). Conclusions The novel index, SLEDAI-2KG, is superior to SLEDAI-2K in identifying responders at 6 and 12 months accounting for steroid dose and thus adjusting for severity within each descriptor of SLEDAI-2K. SLEDAI-2KG has the ability to enhance analyses in clinical trials to differentiate between responders on minimal and moderate/large doses of GC. Disclosure of Interest Z. Touma Grant/research support from: GlaxoSmithKline, D. Gladman: None declared, J. Su: None declared, N. Anderson: None declared, M. Urowitz Grant/research support from: GlaxoSmithKline

  • fri0339 SLEDAI 2k responder index 50 is effective in demonstrating partial response in a phase 2 randomised placebo controlled study of ustekinumab in patients with active systemic lupus erythematosus
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Zahi Touma, Dafna D Gladman, Murray B Urowitz, Marc Chevrier, Carrie Wagner, B Hsu, Shawn Rose, B Zhou, R Gordon
    Abstract:

    Background Ustekinumab (UST), a monoclonal antibody that targets shared p40 subunit of cytokines IL-12 and IL-23, is being investigated in pts w/active systemic lupus erythematosus(SLE). While traditional SLE Disease Activity Index 2000(SLEDAI-2K)scoring assesses complete SLE response for individual disease manifestations, SLEDAI-2K Responder Index-50(S2K RI-50)can be used to evaluate SLE responses using partial improvement(≥50%)in each domain. Objectives To evaluate SLEDAI-2K vs S2K RI-50 response in a randomised, PBO-controlled trial of UST in pts w/active SLE. Methods We conducted a Ph2, PBO-controlled study in adults w/active disease(SLEDAI score ≥6 w/≥1 BILAG A and /or ≥2 BILAG B scores)despite standard-of-care therapy. Pts(n=102)were randomised(3:2) to UST IV~6 mg/kg or PBO at wk0, followed by SC inj of UST 90 mg q8w or PBO beginning at wk8, both added to standard-of-care. We calculated S2K RI-50 response at wk24 using various thresholds to define response including decrease of at least 1,2,3,4,5, or6 points from baseline(BL) in S2K RI-50 score. We also compared proportion of pts w/SLEDAI-2K response vs S2K RI-50 response in pts receiving UST(n=62)vs PBO(n=40)at wk24. Results Change from BL SLEDAI-2K and S2K RI-50 scores were strongly correlated(R=0.89,p Conclusions S2K RI-50 is an instrument that can capture partial clinically important improvement of ≥50% in SLE disease manifestations. The data suggests cutpoints for defining S2K RI-50 response in clinical trials of pts w/moderate-severe SLE disease activity. Disclosure of Interest Z. Touma Grant/research support from: Janssen Research and Development, LLC, M. Urowitz Grant/research support from: Janssen Research and Development, LLC, D. Gladman Grant/research support from: Janssen Research and Development, LLC, C. Wagner Employee of: Janssen Research and Development, LLC, B. Hsu Employee of: Janssen Research and Development, LLC, M. Chevrier Employee of: Janssen Research and Development, LLC, S. Rose Employee of: Janssen Research and Development, LLC, B. Zhou Employee of: Janssen Research and Development, LLC, R. Gordon Employee of: Janssen Research and Development, LLC

L Ines - One of the best experts on this subject based on the ideXlab platform.

  • performance of SLEDAI 2k to detect a clinically meaningful change in sle disease activity a 36 month prospective cohort study of 334 patients
    Lupus, 2019
    Co-Authors: Diogo Jesus, Ana Matos, Carla Henriques, L Ines, Mario Rodrigues, J Pereira A Da Silva
    Abstract:

    ObjectiveThe objective of this paper is to evaluate the performance of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) in detecting clinically meaningful changes in SLE disease ...

  • derivation and validation of the sle disease activity score sle das a new sle continuous measure with high sensitivity for changes in disease activity
    Annals of the Rheumatic Diseases, 2019
    Co-Authors: Diogo Jesus, A Doria, Ana Matos, Carla Henriques, Margherita Zen, Maddalena Larosa, Luca Iaccarino, Jose Antonio Pereira Da Silva, L Ines
    Abstract:

    Objectives To derive and validate a new disease activity measure for systemic lupus erythematosus (SLE), the SLE Disease Activity Score (SLE-DAS), with improved sensitivity to change as compared with SLE Disease Activity Index (SLEDAI), while maintaining high specificity and easiness of use. Methods We studied 520 patients with SLE from two tertiary care centres (derivation and validation cohorts). At each visit, disease activity was scored using the Physician Global Assessment (PGA) and SLEDAI 2000 (SLEDAI-2K). To construct the SLE-DAS, we applied multivariate linear regression analysis in the derivation cohort, with PGA as dependent variable. The formula was validated in a different cohort through the study of: (1) correlations between SLE-DAS, PGA and SLEDAI-2K; (2) performance of SLEDAI-2K and SLE-DAS in identifying a clinically meaningful change in disease activity (ΔPGA≥0.3); and (3) accuracy of SLEDAI-2K and SLE-DAS time-adjusted means in predicting damage accrual. Results The final SLE-DAS instrument included 17 items. SLE-DAS was highly correlated with PGA (r=0.875, p Conclusion SLE-DAS has a good construct validity and has better performance than SLEDAI-2K in identifying clinically significant changes in disease activity and in predicting damage accrual.

  • fri0641 detection of changes in sle disease activity is highly improved with sle das as compared to SLEDAI derivation and preliminary validation of the sle disease activity score sle das
    Annals of the Rheumatic Diseases, 2018
    Co-Authors: Diogo Jesus, A Doria, Ana Matos, Carla Henriques, Margherita Zen, L Ines, D S Jap
    Abstract:

    Background: SLEDAI is a widely used instrument to measure disease activity of systemic lupus erythematosus (SLE). However, it lacks sensitivity to discriminate improvement/worsening as it only scores items categorically and does not include several relevant lupus features, such as hemolytic anemia. Objectives: To derive and validate a SLE Disease Activity Score (SLE-DAS) with improved sensitivity to change, while maintaining the high specificity and simplicity of use of the SLEDAI. Methods: 324 patients fulfilling ACR’97 and/or SLICC’12 classification criteria for SLE and regularly followed at a tertiary care lupus clinic from January 2014 to December 2017 were included. At each outpatient visit, clinical and laboratory data were collected and disease activity (last 30 days) was scored with Physician Global Assessment (PGA) (0–3 scale) and SLEDAI-2K. To derive the SLE-DAS we analyzed data from the study visit with higher disease activity from each patient, applying multivariate linear regression analysis, with PGA as dependent variable/gold-standard. Independent variables tested in the models included items from SLEDAI-2K and continuous variables for swollen joint count, proteinuria, platelet and white blood cells counts. Some features absent from SLEDAI, such as hemolytic anemia, gastrointestinal and cardiopulmonary involvement were added to the model. To assess correlation validity we performed a Spearman’s correlation between the SLE-DAS, PGA and SLEDAI-2K at last follow-up visit. We tested performance of SLEDAI-2K (change ≥4) and SLE-DAS to discriminate a clinically meaningful worsening and improvement in SLE disease activity (change in PGA ≥0.3) using Receiver Operating Characteristic (ROC) curve analysis. We determined the best cut-offs values of SLE-DAS to detect changes in PGA ≥0.3 and calculated the sensitivity, specificity, positive and negative predictive values (PPV, NPV). Statistical significance was set at 0.05. Results: The final SLE-DAS model included 17 items. The SLE-DAS score at last follow-up visit presented high correlation with PGA (rho=0.975, p Conclusions: The SLE-DAS presents good construct validity and much higher discriminative power to detect changes in SLE disease activity as compared to SLEDAI-2K. External validation in another SLE cohort is underway. Disclosure of Interest: None declared

  • op0206 performance of SLEDAI 2k to detect a clinically meaningful change in sle disease activity a 36 month prospective cohort study of 334 patients
    Annals of the Rheumatic Diseases, 2017
    Co-Authors: D Jesus, Carla Henriques, M G V Rodrigues, Arlindo Matos, J A P Da Silva, L Ines
    Abstract:

    Background The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the core determinant of response in the SLE Responder Index (SRI), a primary efficacy outcome in SLE clinical trials. However, SLEDAI is unable to discriminate partial improvement/worsening, as it scores each item categorically. Furthermore, potentially severe lupus manifestations, such as hemolytic anemia are not scored in SLEDAI. Objectives To evaluate the performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity. Methods Prospective cohort study of SLE patients followed at a tertiary care lupus clinic from January 2014 to December 2016. Consecutive patients fulfilling the ACR997 and/or the SLICC912 classification criteria were included. At each outpatient visit, disease activity from the last 30 days was scored in the Physician Global Assessment (PGA) (0–3 cm scale) and in SLEDAI-2k. The association between PGA and SLEDAI-2K at each visit was tested with Spearman9s Correlation. A clinically meaningful change in SLE disease activity was defined as difference in PGA ≥0.3 cm at follow-up compared to the baseline visit. Performance of change in SLEDAI-2K was tested in two models: against worsening and improvement in PGA ≥0.3 cm from baseline using Receiver Operating Characteristic (ROC) curve analysis. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) of SLEDAI-2k to change in PGA was calculated. Statistical significance was set at 0.05. Results We included 334 patients (87.1% female, mean age at baseline - 44.8±14.5 years). At baseline, median PGA and SLEDAI-2k score was 0.2 points (range 0–2.5) and 2 points (range 0–19), respectively. Eighty-three patients (24.8%) had a PGA ≥0.4 points at baseline. During follow-up of 36 months, 2129 visits were performed. PGA and SLEDAI-2K scores presented a high correlation (rho=0.82, p Conclusions SLEDAI-2K presents a limited performance in detecting a clinically meaningful change in SLE disease activity, failing to identify more than a quarter of cases with clinically meaningful improvement or worsening. There is a need to optimize SLE disease activity measures. Disclosure of Interest None declared

Chee Seng Yee - One of the best experts on this subject based on the ideXlab platform.

  • pos0746 the arthritis component of the SLEDAI should only be scored if there is joint swelling
    Annals of the Rheumatic Diseases, 2021
    Co-Authors: Khaled Mahmoud, Chee Seng Yee, David A Isenberg, A Zayat, M Md Y Yusof, K Dutton, L S Teh, David Dcruz, Coziana Ciurtin, P G Conaghan
    Abstract:

    Background: SLE disease activity tools do not optimally define disease activity and response. The SLEDAI arthritis item is common, and sufficient to define SRI response. Lupus patients with arthralgia often have no swelling. Glossary definitions of arthritis in different versions of the SLEDAI have included: swelling, swelling between visits, effusion, tenderness, warmth and erythema. MSK ultrasound in SLE can identify synovitis without swelling, ultrasound synovitis is associated with worse symptoms and serology, predicts response to therapy, and is more responsive to therapy than clinical variables. Objectives: To validate different glossary definitions for SLEDAI arthritis using musculoskeletal ultrasound. Methods: We analysed baseline data from a multicentre longitudinal study. Physicians scored SLEDAI-2K in 133 patients with joint pain that was considered inflammatory, but not necessarily swelling. Stable immunosuppressants and prednisolone =2, and in tendons as >=1 tendon with GS >=1, and abnormal power Doppler as >=1 joint or tendon with PD >=1. Results: 78/133 patients had arthritis scored on SLEDAI-2K. In 21/78, swelling was not a reason for that decision. These 21 patients had either tenderness (16/21), swelling reported between visits (4/21) or both of these (1/21). No patient was scored for warmth, erythema or effusion alone. Comparison of SLEDAI definitions and ultrasound is shown in Table 1. Of 57 patients with SLEDAI arthritis scored due to swelling, 90% had an abnormal ultrasound. The positive predictive value was 89% (95% CI 79 – 94). Of 21 patients with SLEDAI arthritis scored without swelling, 48% had an abnormal ultrasound. The positive predictive value was 48% (95% CI 31 – 67). There was no substantive difference in clinical and serological variables comparing patients with SLEDAI arthritis without swelling and patients without SLEDAI arthritis. In contrast, patients with SLEDAI arthritis with swelling had worse ESR (p=0.0003), Physician MSK disease activity VAS (p Conclusion: Although ultrasound proven synovitis in the absence of swelling is not uncommon, it is not reliably identified using other signs or symptoms. The arthritis item of the SLEDAI was likely to be associated with ultrasound synovitis if scored because of swelling, but not if scored because of tenderness or swelling between visits. Our results support raising the threshold criteria for arthritis so that it should only be scored when there is joint swelling. Previous clinical trial datasets could be re-analysed excluding SLEDAI arthritis scores not confirmed by a swollen joint count greater than one. Disclosure of Interests: Khaled Mahmoud: None declared, Ahmed Zayat: None declared, Md Yuzaiful Md Yusof: None declared, Katherine Dutton: None declared, Lee-Suan Teh: None declared, Chee-Seng Yee: None declared, David d’cruz: None declared, Nora Ng: None declared, David Isenberg: None declared, Coziana Ciurtin: None declared, Philip G Conaghan: None declared, Paul Emery: None declared, Christopher John Edwards Shareholder of: Research grant support from; Abbvie, Biogen, Pfizer, Consultant of: Personal fee from; Abbvie, BMS, Biogen, Celgene, Celltrion, Fresenius, Gilead, GSK, Janssen, Lilly, Mundipharma, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB, Grant/research support from: Research grant support from; Abbvie, Biogen, Pfizer, Elizabeth Hensor: None declared, Edward Vital Speakers bureau: AstraZeneca, Genentech, Aurinia, Lilly, Modus, Consultant of: AstraZeneca, Genentech, Aurinia, Lilly, Modus, Grant/research support from: Sandoz, AstraZeneca,

  • comparison of responsiveness of bilag 2004 SLEDAI 2000 and bilag systems tally bst
    Arthritis Care and Research, 2021
    Co-Authors: Chee Seng Yee, David A Isenberg, Lee Suan Teh, Ian N Bruce, Yasmeen Ahmad, Anisur Rahman, Caroline Gordon, Bridget Griffiths, A Prabu
    Abstract:

    Objective To compare the responsiveness of BILAG‐2004 and SLEDAI‐2000 disease activity indices and determine if there was any added value in combining BILAG‐2004, BILAG System Tally (BST) or simplified BST (sBST) with SLEDAI‐2000. Methods This was a multi‐centre longitudinal study of SLE patients. Data were collected on BILAG‐2004, SLEDAI‐2000 and therapy on consecutive assessments in routine practice. The external responsiveness of the indices was assessed by determining the relationship between change in disease activity and change in therapy between two consecutive visits. Comparison of indices and their derivatives was performed by assessing the main effects of the indices using logistic regression. ROC curves analysis was used to describe the performance of these indices individually and in various combinations and comparisons of AUC were performed. Results There were 1414 observations from 347 patients. Both BILAG‐2004 and SLEDAI‐2000 maintained an independent relationship with change in therapy when compared. There was some improvement in responsiveness when continuous SLEDAI‐2000 variables (change in score and score of previous visit) were combined with BILAG‐2004 system scores. Dichotomisation of BILAG‐2004 or SLEDAI‐2000 resulted in poorer performance. BST and sBST had similar responsiveness as the combination of SLEDAI‐2000 variables and BILAG‐2004 system scores. There was little benefit in combining SLEDAI‐2000 with BST or sBST. Conclusions The BILAG‐2004 index had comparable responsiveness to SLEDAI‐2000. There was some benefit in combining both indices. Dichotomisation of BILAG‐2004 and SLEDAI‐2000 leads to suboptimal performance. BST and sBST performed well on their own; sBST is recommended for its simplicity and clinical meaningfulness.

  • the use of systemic lupus erythematosus disease activity index 2000 to define active disease and minimal clinically meaningful change based on data from a large cohort of systemic lupus erythematosus patients
    Rheumatology, 2011
    Co-Authors: Chee Seng Yee, Vernon T Farewell, David A Isenberg, B Griffiths, Lee Suan Teh, Ian N Bruce, Yasmeen Ahmad, Anisur Rahman, Athiveeraramapandian Prabu, Mohammed Akil
    Abstract:

    Objectives. To examine SLEDAI-2000 cut-off scores for definition of active SLE and to determine the sensitivity to change of SLEDAI-2000 for the assessment of SLE disease activity and minimal clinically meaningful changes in score. Methods. Data from two multi-centre studies were used in the analysis: in a cross-sectional and a longitudinal fashion. At every assessment, data were collected on SLEDAI-2000 and treatment. The cross-sectional analysis with receiver operating characteristic (ROC) curves was used to examine the appropriate SLEDAI-2000 score to define active disease and increase in therapy was the reference standard. In the longitudinal analysis, sensitivity to change of SLEDAI-2000 was assessed with multinomial logistic regression. ROC curves analysis was used to examine possible cut-points in score changes associated with change in therapy, and mean changes were estimated. Results. In the cross-sectional analysis, the most appropriate cut-off scores for active disease were 3 or 4. In the longitudinal analysis, the best model for predicting treatment increase was with the change in SLEDAI-2000 score and the score from the previous visit as continuous variables. The use of cut-points was less predictive of treatment change than the use of continuous score. The mean difference in the change in SLEDAI-2000 scores, adjusted for prior score, between patients with treatment increase and those without was 2.64 (95% CI 2.16, 3.14). Conclusions. An appropriate SLEDAI-2000 score to define active disease is 3 or 4. SLEDAI-2000 index is sensitive to change. The use of SLEDAI-2000 as a continuous outcome is recommended for comparative

  • bilag 2004 index captures systemic lupus erythematosus disease activity better than SLEDAI 2000
    Annals of the Rheumatic Diseases, 2008
    Co-Authors: Chee Seng Yee, David A Isenberg, Lee Suan Teh, Ian N Bruce, Anisur Rahman, Mohammed Akil, Bridget Griffiths, A Prabu, K Sokoll, Neil Mchugh
    Abstract:

    Objective: To assess the reliability of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 index in routine practice and its ability to capture disease activity as compared with the British Isles Lupus Assessment Group (BILAG)-2004 index. Methods: Patients with systemic lupus erythematosus from 11 centres were assessed separately by two raters in routine practice. Disease activity was assessed using the BILAG-2004 and SLEDAI-2000 indices. The level of agreement for items was used to assess the reliability of SLEDAI-2000. The ability to detect disease activity was assessed by determining the number of patients with a high activity on BILAG-2004 (overall score A or B) but low SLEDAI-2000 score ( Results: 93 patients (90.3% women, 69.9% Caucasian) were studied: mean age was 43.8 years, mean disease duration 10 years. There were 43 patients (46.2%) with a difference in SLEDAI-2000 score between the two raters and this difference was ⩾4 in 19 patients (20.4%). Agreement for each of the items in SLEDAI-2000 was between 81.7 and 100%. 35 patients (37.6%) had high activity on BILAG-2004 but a low SLEDAI-2000 score, of which 48.6% had treatment increased. There were only five patients (5.4%) with low activity on BILAG-2004 but a high SLEDAI-2000 score. Conclusions: SLEDAI-2000 is a reliable index to assess systemic lupus erythematosus disease activity but it is less able than the BILAG-2004 index to detect active disease requiring increased treatment.

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