Article Figures & Data
Figures
- Figure 1.
Patient disposition. a Patients who discontinued study treatment were considered to have withdrawn due to patient decision if other possible underlying causes such as adverse events or lack of efficacy were excluded. b Patients who chose to stop participating in the study and wanted no further visits or assessments and no further study-related contact were considered to have withdrawn consent. c One patient discontinued treatment period 2 before receiving study drug due to a positive pregnancy test.
- Figure 2.
(A) ACR20, (B) ACR50, and (C) ACR70 response rates through week 52. a Includes patients with uptitration to secukinumab 300 mg at weeks 16, 28, or 40. * P < 0.05; statistically significant odds ratio in favor of secukinumab dose vs placebo based on logistic regression using nonresponder imputation. ACR: American College of Rheumatology.
- Figure 3.
(A) ACR, (B) enthesitis, (C) dactylitis, and (D) MDA responses at any timepoint between weeks 16 and 52 following uptitration from secukinumab 150 mg to 300 mg among nonresponders.a a Patients defined as nonresponders were those who had < 20% improvement from baseline in both tender and swollen joint counts, at weeks 16, 28, or 40. Unless otherwise noted, these analyses included all patients with uptitration from secukinumab 150 mg to 300 mg and completed the study. b Patients included in the LEI + SPARCC subset were included in this analysis. c Patients included in the dactylitis subset were included in this analysis. d MDA is defined as achievement of ≥ 5 of the following 7 criteria: tender joint count ≤ 1; swollen joint count ≤ 1; Psoriasis Area and Severity Index ≤ 1 or body surface area ≤ 3; patient pain VAS ≤ 15; patient global disease activity VAS ≤ 20; Health Assessment Questionnaire ≤ 0.5; tender entheseal points ≤ 1. ACR: American College of Rheumatology; LEI: Leeds Enthesitis Index, MDA: minimal disease activity; SPARCC: Spondyloarthritis Research Consortium of Canada Enthesitis Index; VAS: visual analog scale.
Tables
SEC 300 mg, n = 103 SEC 150 mg, n = 103 Placebo, n = 52 Age, yrs Mean (SD) 51.9 (12.6) 51.3 (14.6) 53.1 (12.7) Median (min, max) 53.0 (29, 82) 52.0 (19, 80) 56.0 (20, 74) Male sex, n (%) 53 (51.5) 56 (54.4) 23 (44.2) Race, n (%) White 88 (85.4) 88 (85.4) 45 (86.5) Black 2 (1.9) 2 (1.9) 3 (5.8) Asian 9 (8.7) 10 (9.7) 1 (1.9) Native American 0 1 (1.0) 1 (1.9) Pacific Islander 1 (1.0) 1 (1.0) 0 Other 2 (1.9) 0 2 (3.8) Unknown 1 (1.0) 1 (1.0) 0 Weight, kg, mean (SD) 93.4 (23.0) 86.9 (23.3) 97.2 (26.5) BMI, kg/m2, mean (SD) 32.8 (8.2) 30.7 (7.6) 34.1 (7.8) 10th percentile 23.7 21.9 24.9 25th percentile 26.4 25.4 27.8 50th percentile 32.4 29.0 32.4 75th percentile 38.1 35.1 40.7 90 th percentile 42.8 40.7 44.9 Time since first PsA diagnosis, yrs, mean (SD) 3.0 (4.4) 3.8 (5.6) 3.9 (5.0) Methotrexate use, n (%) 34 (33.0) 23 (22.3) 18 (34.6) Dose, mg/week, mean (SD) 17.1 (4.6) 16.4 (4.2) 16.3 (6.1) Corticosteroid use, n (%) 12 (11.7) 11 (10.7) 3 (5.8) NSAID use, n (%) 33 (32.0) 35 (34.0) 18 (34.6) Presence of dactylitis, LDI, n (%) 49 (47.6) 52 (50.5) 23 (44.2) Presence of enthesitis, SPARCC + LEI, n (%) 74 (71.8) 76 (73.8) 39 (75.0) TJC78, mean (SD) 27.1 (19.6) 25.6 (18.6) 25.2 (15.0) SJC76, mean (SD) 17.7 (16.4) 14.4 (13.9) 13.8 (11.9) PASI score, mean (SD) 8.3 (8.0) 9.0 (10.0) 5.9 (5.4) DAS28-CRP score, mean (SD) 4.9 (1.2) 4.7 (1.3) 5.0 (1.1) PASDAS score, mean (SD) 6.2 (1.3) 6.0 (1.3) 6.2 (1.3) SF-12 MCS, mean (SD) 46.5 (11.0) 45.7 (10.8) 46.0 (11.6) SF-12 PCS, mean (SD) 36.9 (10.1) 38.3 (9.7) 35.9 (8.8) HAQ-DI, mean (SD) 1.1 (0.6) 1.0 (0.6) 1.3 (0.7) RAPID3, mean (SD) 14.6 (5.6) 13.9 (5.7) 15.6 (5.7) DAS28-CRP: Disease Activity Score in 28 joints using C-reactive protein; HAQ-DI: Health Assessment Questionnaire-Disability Index; LDI: Leeds Dactylitis Index; LEI: Leeds Enthesitis Index; NSAID: nonsteroidal antiinflammatory drug; MCS: mental component summary score; PASI: Psoriasis Area and Severity Index; PASDAS: Psoriatic Arthritis Disease Activity Score; PCS: physical component summary score; PsA: psoriatic arthritis; RAPID3: Routine Assessment of Patient Index Data 3; SF-12: 12-item Short Form Health Survey; SEC: secukinumab; SJC76: swollen joint count in 76 joints; SPARCC: Spondyloarthritis Research Consortium of Canada Enthesitis Index; TJC78: tender joint count in 78 joints.
- Table 2.
Summary of primary and key secondary and exploratory efficacy results at week 16a.
Outcome Placebo, n = 52, n/N (%) SEC, 300 mg, n = 103, n/N (%) OR
(95% CI)P SEC 150 mg, n = 103, n/N (%) OR
(95% CI)P Primary efficacy variable ACR20 12/52 (23.1) 53/103 (51.5) 3.51 (1.65-7.45) 0.001 38/103 (36.9) 1.92 (0.89-4.15) 0.10 Secondary binary efficacy variables ACR50 3/52 (5.8) 29/103 (28.2) 6.30 (1.81-21.88) 0.004 25/103 (24.3) 4.77 (1.36-16.77) 0.02 ACR70 1/52 (1.9) 18/103 (17.5) 10.50 (1.36-81.30) 0.02 11/103 (10.7) 5.42 (0.67-43.64) 0.11 Resolution of enthesitis, LEI + SPARCCb 7/39 (17.9) 28/74 (37.8) 2.85 (1.08-7.50) 0.03 30/76 (39.5) 2.65 (1.01-6.93) 0.047 Resolution of dactylitisc 4/23 (17.4) 20/49 (40.8) 3.27 (0.96-11.20) 0.06 20/52 (38.5) 3.40 (0.98-11.76) 0.05 PASI75d 7/43 (16.3) 51/79 (64.6) 9.49 (3.73-24.16) < 0.001 45/83 (54.2) 6.38 (2.51-16.24) < 0.001 PASI90d 4/43 (9.3) 39/79 (49.4) 9.86 (3.19-30.45) < 0.001 30/83 (36.1) 5.21 (1.68-16.21) 0.004 PASI100d 1/43 (2.3) 20/79 (25.3) 14.38 (1.86-111.53) 0.01 15/83 (18.1) 9.82 (1.24-77.90) 0.03 MDA 2/52 (3.8) 27/103 (26.2) 8.75 (1.99-38.45) 0.004 27/103 (26.2) 8.34 (1.89-36.85) 0.005 Placebo, LSM, n = 52 SEC 300 mg, LSM, n = 103 LSM of Treatment Difference, (SE)e [95% CI] P SEC 150 mg, LSM, n = 103 LSM of Treatment Difference, (SE)e [95% CI] P Secondary and exploratory continuous efficacy variablesf Change from baseline in DAS28-CRP -0.35 -1.39 -1.05 (0.203)
[-1.45 to -0.65]< 0.001 -1.18 -0.83 (0.207)
[-1.24 to -0.43]< 0.001 Change from baseline in PASDAS -0.36 -1.04 -0.68 (0.085)
[-0.85 to -0.52]< 0.001 -0.92 -0.57 (0.086)
[-0.74 to -0.40]< 0.001 Change from baseline in SF-12 MCS 1.54 3.05 1.51 (1.334)
[-1.12 to 4.14]0.26 1.77 0.23 (1.353)
[-2.43 to 2.90]0.86 Change from baseline in SF-12 PCS -0.63 4.82 5.45 (1.363)
[2.76 to 8.13]< 0.001 4.32 4.94 (1.385)
[2.22 to 7.67]< 0.001 Change from baseline in HAQ-DI -0.11 -0.32 -0.21 (0.081)
[-0.37 to -0.05]0.01 -0.24 -0.13 (0.083)
[-0.30 to 0.03]0.11 Change from baseline in RAPID3 -0.78 -4.57 -3.80 (0.941)
[-5.65 to -1.94]< 0.001 -3.67 -2.89 (0.960)
[-4.78 to -1.00]0.003 ↵aORs, 95% CIs, and P values are based on logistic regression using nonresponder imputation.
↵bResults are from the combined LEI and SPARCC subset. Enthesitis was determined in patients who had an enthesitis score ≥ 1 when sites from LEI and SPARCC were assessed together at baseline: SEC 300 mg, n = 74; SEC 150 mg, n = 76; placebo, n = 39.
↵cDactylitis was determined in patients who had a Leeds Dactylitis Index ≥ 1 at baseline: SEC 300 mg, n = 49; SEC 150 mg, n = 52; placebo, n = 23.
↵dResults are from patients having psoriatic skin involvement in ≥ 3% of their body surface area at baseline: SEC 300 mg, n = 79; SEC 150 mg, n = 83; placebo, n = 43.
↵eLSM of the treatment difference vs placebo.
↵fLSM, LSM of treatment differences, 95% CI, and P values are based on an ANCOVA model; missing data were imputed using last observation carried forward.
ACR: American College of Rheumatology; DAS28-CRP: Disease Activity Score in 28 joints using C-reactive protein; HAQ-DI: Health Assessment Questionnaire-Disability Index; LEI: Leeds Enthesitis Index; LSM: least-squares mean; MCS: mental component summary score; MDA: minimal disease activity; OR: odds ratio; PASDAS: Psoriatic Arthritis Disease Activity Score; PASI: Psoriasis Area and Severity Index; PCS: physical component summary score; RAPID3: Routine Assessment of Patient Index Data 3; SE: standard error; SEC: secukinumab; SF-12: 12-item Short Form Health Survey; SPARCC: Spondyloarthritis Research Consortium of Canada Enthesitis Index.
Patients with AEs, n (%) SEC 300 mg, n = 103 SEC 150 mg, n = 103 Placebo, n = 52 Any AE 59 (57.3) 61 (59.2) 27 (51.9) Serious AEs 2 (1.9) 2 (1.9) 2 (3.8) Death 0 0 1 (1.9) Discontinuation due to AEs 1 (1.0) 1 (1.0) 0 Common AEs (≥ 3% in any treatment group) Diarrhea 6 (5.8) 6 (5.8) 1 (1.9) Upper respiratory tract infection 6 (5.8) 2 (1.9) 0 Hypertension 5 (4.9) 4 (3.9) 0 Sinus congestion 4 (3.9) 0 0 Fatigue 3 (2.9) 5 (4.9) 0 Headache 3 (2.9) 4 (3.9) 2 (3.8) Nasopharyngitis 3 (2.9) 4 (3.9) 1 (1.9) Abdominal pain 2 (1.9) 2 (1.9) 2 (3.8) Musculoskeletal pain 2 (1.9) 1 (1.0) 3 (5.8) Sinusitis 2 (1.9) 1 (1.0) 2 (3.8) Arthralgia 1 (1.0) 2 (1.9) 4 (7.7) Back pain 1 (1.0) 4 (3.9) 0 Pain in extremity 1 (1.0) 3 (2.9) 3 (5.8) Peripheral edema 1 (1.0) 0 2 (3.8) Psoriasis 1 (1.0) 4 (3.9) 0 Psoriatic arthropathy 1 (1.0) 4 (3.9) 0 Respiratory tract congestion 0 0 2 (3.8) Selected AEs of interest Candidiasis Candida infection 1 (1.0) 2 (1.9) 0 Skin Candida 0 1 (1.0) 0 Major cardiac AEs Myocardial infarction 0 1 (1.0) 0 Ischemic stroke 0 0 1 (1.9) Neutropenia 1 (1.0) 0 0 Values are expressed as n (%) unless otherwise stated. AE: adverse event; SEC: secukinumab.
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