Why carry out this study?
|
There is little real-world data describing whether the effectiveness of ixekizumab for the treatment of psoriasis among patients for whom biologic therapy has failed differs by prior biologic status. |
We compared the 6-month effectiveness of ixekizumab between patients who previously failed secukinumab and those who failed other biologics among patients in the CorEvitas Psoriasis Registry. |
We hypothesized that (1) clinical outcomes and patient-reported outcomes (PROs) will improve following a switch to ixekizumab, and (2) there will be no differences in responses between patients who previously failed secukinumab and those who failed other biologics. |
What was learned from the study?
|
These findings suggest that real-world patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvement in disease severity at 6-month follow-up. |
Our findings that patients who switch to ixekizumab, regardless of failure or non-failure on other biologics, experience improved skin clearance, is evidence clinicians can use when treating both types of patients. |
Our up-to-date research provides evidence for patient health education and confirmation that outcomes can improve following a biologic switch. |
Introduction
Methods
Registry Overview
Study Population
Variables
Prior Biologic Status
Outcomes
Disease Activity Measures
Patient-reported Outcomes (PROs)
Other Variables
Statistical Analysis
Patient Characteristics at IXE Initiation
Six-month Outcomes Among Prior Biologic Groups
Likelihood of Response in Other Biologic Failure vs. SEC Failure
Ethics
Results
Patient Characteristics at IXE Initiation
Secukinumab | Other Biologic | Overall | |||||
---|---|---|---|---|---|---|---|
Total | Prior SEC failure | Prior SEC non-failure | Total | Prior other BIO failure | Prior other BIO non-failure | Total | |
N = 136 | N = 108 | N = 28 | N = 283 | N = 200 | N = 83 | N = 419 | |
Demographic/socioeconomic characteristics | |||||||
Age in years | n = 136 | n = 108 | n = 28 | n = 283 | n = 200 | n = 83 | n = 419 |
Mean (SD) | 50.4 (12.6) | 50.1 (13.1) | 51.6 (10.7) | 51.6 (13.1) | 50.8 (13.1) | 53.4 (13.0) | 51.2 (12.9) |
Gender—Female | 64/136 (47.1%) | 52/108 (48.1%) | 12/28 (42.9%) | 139/283 (49.1%) | 99/200 (49.5%) | 40/83 (48.2%) | 203/419 (48.4%) |
Race—White | 106/136 (77.9%) | 83/108 (76.9%) | 23/28 (82.1%) | 237/283 (83.7%) | 168/200 (84.0%) | 69/83 (83.1%) | 343/419 (81.9%) |
Type of health insurance plana | |||||||
Private, n (%) | 103/135 (76.3%) | 83/107 (77.6%) | 20/28 (71.4%) | 223/277 (80.5%) | 158/195 (81.0%) | 65/82 (79.3%) | 326/412 (79.1%) |
Medicare, n (%) | 23/135 (17.0%) | 18/107 (16.8%) | 5/28 (17.9%) | 46/277 (16.6%) | 25/195 (12.8%) | 21/82 (25.6%) | 69/412 (16.7%) |
Education | |||||||
No college, n (%) | 86/136 (63.2%) | 67/108 (62.0%) | 19/28 (67.9%) | 165/283 (58.3%) | 118/200 (59.0%) | 47/83 (56.6%) | 251/419 (59.9%) |
College graduate or higher, n (%) | 50/136 (36.8%) | 41/108 (38.0%) | 9/28 (32.1%) | 118/283 (41.7%) | 82/200 (41.0%) | 36/83 (43.4%) | 168/419 (40.1%) |
Lifestyle characteristics | |||||||
Smoking history | |||||||
Never smoker, n (%) | 56/136 (41.2%) | 46/108 (42.6%) | 10/28 (35.7%) | 127/281 (45.2%) | 89/198 (44.9%) | 38/83 (45.8%) | 183/417 (43.9%) |
Former smoker, n (%) | 53/136 (39.0%) | 40/108 (37.0%) | 13/28 (46.4%) | 106/281 (37.7%) | 70/198 (35.4%) | 36/83 (43.4%) | 159/417 (38.1%) |
Current smoker, n (%) | 27/136 (19.9%) | 22/108 (20.4%) | 5/28 (17.9%) | 48/281 (17.1%) | 39/198 (19.7%) | 9/83 (10.8%) | 75/417 (18.0%) |
BMI (body mass index) in kg/m2 | n = 136 | n = 108 | n = 28 | n = 283 | n = 197 | n = 83 | n = 416 |
Mean (SD) | 33.8 (8.4) | 33.3 (7.7) | 35.7 (10.6) | 32.3 (8.0) | 32.6 (8.5) | 31.5 (6.7) | 32.8 (8.2) |
History of comorbiditiesa | |||||||
Cardiovascular diseaseb, n (%) | 11/136 (8.1%) | 10/108 (9.3%) | 1/28 (3.6%) | 35/283 (12.4%) | 24/200 (12.0%) | 11/83 (13.3%) | 46/419 (11.0%) |
Hypertension, n (%) | 59/136 (43.4%) | 48/108 (44.4%) | 11/28 (39.3%) | 125/283 (44.2%) | 89/200 (44.5%) | 36/83 (43.4%) | 184/419 (43.9%) |
Hyperlipidemia, n (%) | 46/36 (33.8%) | 39/108 (36.1%) | 7/28 (25.0%) | 93/283 (32.9%) | 63/200 (31.5%) | 30/83 (36.1%) | 13/4199 (33.2%) |
Diabetes mellitus, n (%) | 25/136 (18.4%) | 21/108 (19.4%) | 4/28 (14.3%) | 54/283 (19.1%) | 33/200 (16.5%) | 21/83 (25.3%) | 79/419 (18.9%) |
Disease characteristics | |||||||
Psoriasis morphologya | |||||||
Plaque, n (%) | 135/136 (99.3%) | 108/108 (100.0%) | 27/28 (96.4%) | 275/283 (97.2%) | 194/200 (97.0%) | 81/83 (97.6%) | 410/419 (97.9%) |
Palmoplantar, n (%) | 16/136 (11.8%) | 13/108 (12.0%) | 3/28 (10.7%) | 41/283 (14.5%) | 29/200 (14.5%) | 12/83 (14.5%) | 57/419 (13.6%) |
Inverse/intertriginous, n (%) | 19 (14.0%) | 15/108 (13.9%) | 4/28 (14.3%) | 24 (8.5%) | 19/200 (9.5%) | 5/83 (6.0%) | 43/419 (10.3%) |
Scalp, n (%) | 56/136 (41.2%) | 44/108 (40.7%) | 12/28 (42.9%) | 99/283 (35.0%) | 66/200 (33.0%) | 33/83 (39.8%) | 155/419 (37.0%) |
Nail, n (%) | 38/136 (27.9%) | 31/108 (28.7%) | 7/28 (25.0%) | 150/283 (53.0%) | 36/200 (18.0%) | 17/83 (20.5%) | 91/419 (21.7%) |
Duration of psoriasis disease in years | n = 136 | n = 108 | n = 28 | n = 283 | n = 200 | n = 83 | n = 419 |
Mean (SD) | 19.2 (12.5) | 19.6 (12.8) | 17.5 (11.4) | 18.4 (12.6) | 18.5 (13.0) | 18.4 (11.8) | 18.7 (12.6) |
Psoriatic arthritis, n (%) | 75/136 (55.1%) | 62/108 (57.4%) | 13/28 (46.4%) | 150/283 (53.0%) | 104/200 (52.0%) | 46/83 (55.4%) | 225/419 (53.7%) |
Psoriasis-specific measures | |||||||
BSA (% involvement) | n = 136 | n = 108 | n = 28 | n = 283 | n = 200 | n = 83 | n = 419 |
Mean (SD) | 10.4 (11.0) | 9.4 (8.6) | 13.9 (17.3) | 11.6 (14.2) | 11.8 (14.7) | 11.3 (12.8) | 11.2 (13.2) |
BSA – categorical, n (%) | |||||||
Mild disease [0, 3] | 28/136 (20.6%) | 20/108 (18.5%) | 8/28 (28.6%) | 57/283 (20.1%) | 42/200 (21.0%) | 15/83 (18.1%) | 85/419 (20.3%) |
Moderate disease [3. 10] | 67/136 (49.3%) | 59/108 (54.6%) | 8/28 (28.6%) | 133/283 (47.0%) | 92/200 (46.0%) | 41/83 (49.4%) | 200/419 (47.7%) |
Severe disease [0, 100] | 41/136 (30.1%) | 29/108 (26.9%) | 12/28 (42.9%) | 93/283 (32.9%) | 66/200 (33.0%) | 27/83 (32.5%) | 134/419 (32.0%) |
PASI (score: 0–72) | n = 136 | n = 108 | n = 28 | n = 136 | n = 200 | n = 83 | n = 419 |
Mean (SD) | 7.6 (6.5) | 7.5 (5.8) | 7.9 (9.0) | 7.6 (6.5) | 7.7 (7.5) | 7.7 (6.5) | 7.7 (7.0) |
PASI—categorical | |||||||
PASI ≤ 10, n (%) | 101/136 (74.3%) | 81/108 (75.0%) | 20/28 (71.4%) | 201/283 (71.0%) | 140/200 (70.0%) | 61/83 (73.5%) | 302/419 (72.1%) |
PASI > 10, n (%) | 35/136 (25.7%) | 27 (25.0%) | 8 (28.6%) | 82/283 (29.0%) | 60 (30.0%) | 22 (26.5%) | 117 (27.9%) |
IGA (score: 0–5) | n = 136 | n = 108 | n = 28 | n = 283 | n = 200 | n = 83 | n = 419 |
Mean (SD) | 3.9 (0.7) | 4.0 (0.7) | 3.8 (0.8) | 3.8 (0.9) | 3.8 (0.8) | 3.8 (1.0) | 3.8 (0.8) |
PEST, n (%) | |||||||
Negative screen (< 3) | 80/133 (60.2%) | 63/105 (60.0%) | 17/28 (60.7%) | 171/274 (62.4%) | 120/195 (61.5%) | 51/79 (64.6%) | 251/407 (61.7%) |
Positive screen (≥ 3) | 53/133 (39.8%) | 42/105 (40.0%) | 11/28 (39.3%) | 103/274 (37.6%) | 75/195 (38.5%) | 28/79 (35.4%) | 156/407 (38.3%) |
Secukinumab | Other Biologic | Overall | |||||
---|---|---|---|---|---|---|---|
Total | Prior SEC failure | Prior SEC non-failure | Total | Prior other BIO failure | Prior other BIO non-failure | Total | |
N = 136 | N = 108 | N = 28 | N = 283 | N = 200 | N = 83 | N = 419 | |
Treatment characteristics | |||||||
Concomitant therapiesa | |||||||
Non-biologic systemics, n (%) | 10/108 (9.3%) | 10/108 (9.3%) | 2/28 (7.1%) | 27/283 (9.5%) | 18/200 (9.0%) | 9/83 (10.8%) | 39/419 (9.3%) |
Phototherapy, n (%) | 3/108 (2.8%) | 3/108 (2.8%) | 0/28 (0.0%) | 6/283 (2.1%) | 4/200 (2.0%) | 2/83 (2.4%) | 9/419 (2.1%) |
Topical agents, n (%) | 38/108 (35.2%) | 38/108 (35.2%) | 9/28 (32.1%) | 134/283 (47.3%) | 99/200 (49.5%) | 35/83 (42.2%) | 181/419 (43.2%) |
Previous biologic therapies, n (%) | n = 108 | n = 108 | n = 28 | n = 283 | n = 200 | n = 83 | n = 419 |
1 | 15 (13.9%) | 15 (13.9%) | 6 (21.4%) | 124/283 (43.8%) | 82 (41.0%) | 42 (50.6%) | 145 (34.6%) |
2+ | 93 (86.1%) | 93 (86.1%) | 22 (78.6%) | 159/283 (56.2%) | 118 (59.0%) | 41 (49.4%) | 274 (65.4%) |
Specific previous biologic therapies receiveda | |||||||
TNFi, n (%) | 87/108 (80.6%) | 87/108 (80.6%) | 20/28 (71.4%) | 253/283 (89.4%) | 181/200 (90.5%) | 72/83 (86.7%) | 360/419 (85.9%) |
IL-17, n (%) | 108/108 (100.0%) | 108/108 (100.0%) | 28/28 (100.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 136/419 (32.5%) |
IL-12/23, n (%) | 51/108 (47.2%) | 51/108 (47.2%) | 14/28 (50.0%) | 131/283 (46.3%) | 100/200 (50.0%) | 31/83 (37.3%) | 196/419 (46.8%) |
IL-23, n (%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 12/283 (4.2%) | 10/200 (5.0%) | 2/83 (2.4%) | 12/419 (2.9%) |
Previous non-biologic systemic therapies, n (%) | |||||||
0 | 41/136 (30.1%) | 31/108 (28.7%) | 10/28 (35.7%) | 111/283 (39.2%) | 76/200 (38.0%) | 35/83 (42.2%) | 152/419 (36.3%) |
1 | 56/136 (41.2%) | 42/108 (38.9%) | 14/28 (50.0%) | 117/283 (41.3%) | 84/200 (42.0%) | 33/83 (39.8%) | 173/419 (41.3%) |
2 + | 39/136 (28.7%) | 35/108 (32.4%) | 4/28 (14.3%) | 55/283 (19.4%) | 40/200 (20.0%) | 15/83 (18.1%) | 94/419 (22.4%) |
Patient-reported outcomes | |||||||
DLQI (score: 0–30) | n = 136 | n = 108 | n = 28 | n = 283 | n = 200 | n = 83 | n = 419 |
Mean (SD) | 7.7 (6.3) | 7.4 (5.8) | 8.8 (7.8) | 7.5 (6.2) | 7.1 (5.8) | 8.4 (7.1) | 7.6 (6.2) |
WPAI summary scores | |||||||
Currently employed, n (%) | 92/136 (67.6%) | 73/108 (67.6%) | 19/28 (67.9%) | 209/283 (73.9%) | 150/200 (75.0%) | 59/83 (71.1%) | 301/419 (71.8%) |
Absenteeismb | n = 88 | n = 70 | n = 18 | n = 190 | n = 138 | n = 52 | n = 278 |
Mean (SD) | 1.7 (2.7) | 1.4 (1.7) | 2.9 (4.7) | 2.5 (4.1) | 2.4 (4.0) | 2.7 (4.6) | 2.3 (3.7) |
Presenteeismb | n = 88 | n = 70 | n = 18 | n = 189 | n = 136 | n = 53 | n = 277 |
Mean (SD) | 8.5 (9.2) | 8.2 (8.8) | 9.9 (10.5) | 8.9 (10.4) | 8.3 (9.8) | 10.5 (11.8) | 8.8 (10.0) |
Work productivity lossb | n = 88 | n = 70 | n = 18 | n = 186 | n = 135 | n = 51 | n = 274 |
Mean (SD) | 10.4 (11.8) | 9.8 (10.9) | 12.7 (14.8) | 11.1 (13.5) | 10.3 (12.8) | 13.4 (15.1) | 10.9 (12.9) |
Activity impairment | n = 135 | n = 107 | n = 28 | n = 280 | n = 198 | n = 82 | n = 415 |
Mean (SD) | 16.3 (14.9) | 15.4 (14.7) | 20.0 (15.1) | 15.3 (15.1) | 15.0 (14.7) | 16.0 (16.1) | 15.7 (15.0) |
Patient global assessment | n = 135 | n = 107 | n = 28 | n = 283 | n = 200 | n = 83 | n = 418 |
Mean (SD) | 47.9 (27.6) | 48.4 (26.5) | 46.1 (32.3) | 47.8 (28.7) | 45.4 (27.4) | 53.8 (31.0) | 47.9 (28.3) |
Patient overall itch/pruritis (VAS range 0–100) | n = 135 | n = 107 | n = 28 | n = 283 | n = 200 | n = 83 | n = 418 |
Mean (SD) | 51.7 (33.1) | 52.6 (32.7) | 48.2 (35.0) | 48.6 (33.7) | 47.1 (32.4) | 52.1 (36.8) | 49.6 (33.5) |
Patient overall fatigue (VAS range 0–100) | n = 135 | n = 107 | n = 28 | n = 283 | n = 200 | n = 83 | n = 418 |
Mean (SD) | 40.9 (31.4) | 40.7 (31.6) | 41.5 (31.1) | 37.7 (29.3) | 35.0 (27.9) | 44.1 (31.9) | 38.7 (30.0) |
Patient overall skin pain (VAS range 0–100) | n = 135 | n = 107 | n = 28 | n = 283 | n = 200 | n = 83 | n = 418 |
Mean (SD) | 38.3 (32.9) | 38.8 (31.9) | 36.1 (36.9) | 30.8 (31.1) | 29.4 (29.0) | 34.3 (35.6) | 33.2 (31.8) |
Patient health state today (EQ-5D-3L VAS range 0–100) | n = 136 | n = 108 | n = 28 | n = 282 | n = 199 | n = 83 | n = 418 |
Mean (SD) | 70.8 (21.2) | 71.9 (20.4) | 66.5 (23.9) | 68.5 (21.5) | 69.5 (19.8) | 66.2 (25.2) | 69.3 (21.4) |
Six-month Outcomes Among Prior Biologic Groups
Prior SEC failure | Prior SEC non-failure | Prior other BIO failure | Prior other BIO non-failure | Total | |
---|---|---|---|---|---|
Discontinued IXE at time of follow-up visit | n = 108 | n = 28 | n = 200 | n = 83 | n = 419 |
n (%) | 22 (20.4%) | 5 (17.9%) | 45 (22.5%) | 20 (24.1%) | 92 (22.0%) |
Primary reason for discontinuationa | n = 22 | n = 4 | n = 42 | n = 19 | n = 87 |
Efficacy | 14 (63.6%) | 2 (50.0%) | 20 (47.6%) | 2 (10.5%) | 38 (43.7%) |
Safety | 1 (4.5%) | 0 (0.0%) | 8 (19.0%) | 3 (15.8%) | 12 (13.8%) |
Insurance | 2 (9.1%) | 0 (0.0%) | 3 (7.1%) | 4 (21.1%) | 9 (10.3%) |
Active disease | 0 (0.0%) | 1 (25.0%) | 0 (0.0%) | 2 (10.5%) | 3 (3.4%) |
Other reasons | 5 (22.7%) | 1 (25.0%) | 11 (26.2%) | 8 (42.1%) | 25 (28.7%) |
Likelihood of Response in Other Biologic Failure vs. SEC Failure
Outcome | Difference in mean change of patient-reported outcomes for other biologic failure group relative to secukinumab failure group | |||
---|---|---|---|---|
Unadjusted | Adjusted a | |||
β (95% CI) | p valueb | β (95% CI) | p valueb | |
Patient-reported outcomes | ||||
Itch | − 1.10 (− 9.76, 7.56) | 0.804 | − 4.34 (− 11.59, 2.91) | 0.241 |
Fatigue | − 2.72 (− 9.69, 4.25) | 0.445 | − 5.00 (− 11.00, 1.01) | 0.104 |
Pain | − 1.10 (− 9.76, 7.56) | 0.804 | − 5.17 (− 13.83, 3.48) | 0.242 |
Patient Global Assessment | − 1.80 (− 9.62, 6.01) | 0.652 | − 2.77 (− 9.31, 3.78) | 0.408 |
EQ-5D-3L VAS | 2.08 (− 2.48, 6.65) | 0.372 | − 0.01 (− 3.89, 3.88) | 0.998 |
WPAI | ||||
Absenteeismc | − 0.24 (− 1.47, 0.99) | 0.702 | 0.88 (− 0.11, 1.88) | 0.084 |
Presenteeismc | − 1.49 (− 4.25, 1.28) | 0.294 | − 1.06 (− 3.02, 0.91) | 0.294 |
Work productivity lossc | − 2.09 (− 5.80, 1.63) | 0.272 | − 1.13 (− 3.97, 1.71) | 0.437 |
Activity impairment | − 2.36 (− 5.56, 0.85) | 0.150 | − 2.15 (− 4.58, 0.29) | 0.085 |