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The Effect of Bodyweight On The Efficacy and Safety of Ixekizumab PDF
The Effect of Bodyweight On The Efficacy and Safety of Ixekizumab PDF
The Effect of Bodyweight On The Efficacy and Safety of Ixekizumab PDF
14252 JEADV
ORIGINAL ARTICLE
Abstract
Background There is concern that increased bodyweight may impact efficacy of some therapies used to treat psoria-
sis.
Objective To evaluate the effect of bodyweight on response to ixekizumab treatment in patients with moderate-to-
severe psoriasis.
Methods Patients were characterized under three bodyweight categories (<80 kg, 80 to <100 kg, ≥100 kg) in this pre-
planned subgroup analysis from an integrated database of three multicenter, randomised, double-blind, controlled
Phase 3 clinical studies (UNCOVER-1, UNCOVER-2 and UNCOVER-3). In the first 12 weeks of each study, patients were
randomly assigned to receive subcutaneous placebo, 80-mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE
Q4W) after a starting dose of 160-mg ixekizumab, or 50-mg etanercept twice weekly (UNCOVER-2 and UNCOVER-3
only).
Results This analysis included 3855 patients with baseline bodyweight in the IXE Q4W (N = 1159), IXE Q2W
(N = 1168), placebo (N = 789) and etanercept (N = 739) groups. Distribution of patients across bodyweight categories
was similar between treatment groups. Baseline demographics and patients characteristics were generally consistent
across treatment groups within each bodyweight category. Across all bodyweight categories, a significantly higher
percentage of patients treated with IXE Q2W or IXE Q4W than with placebo or etanercept achieved PASI 75, PASI 90 or
PASI 100 at Week 12. No meaningful differences in PASI 75 response rates were observed across bodyweight cate-
gories. Some numerical differences in PASI 90 and PASI 100 response rates were observed between bodyweight cate-
gories with IXE Q2W providing numerically higher response rates than IXE Q4W. The incidence of treatment-emergent
adverse events was similar in the treatment groups and across bodyweight categories.
Conclusion Ixekizumab was efficacious in the treatment of moderate-to-severe psoriasis regardless of bodyweight.
The safety profile of ixekizumab was also similar across bodyweight categories, and no safety signals were identified
specific to any of the bodyweight categories.
Received: 21 December 2016; Accepted: 14 February 2017
Conflicts of interest
Prof. Reich has participated on an advisory board (honoraria) for Abbvie, Amgen, Biogen, Boehringer Ingelheim
Pharma, Celgene, Forward Pharma, Janssen-Cilag, Leo, Eli Lilly and Company, Novartis, Pfizer, Regeneron,
Takeda, UCB Pharma, and Xenoport. He has also participated as a speaker/faculty education (honoraria) for
Abbvie, Celgene, Covagen, Janssen-Cilag, Leo, Eli Lilly and Company, Medac, Merck Sharp & Dohme Corp.,
and Novartis, has participated as an author (no compensation) for Abbvie, Biogen, Celgene, Forward Pharma,
GlaxoSmithKline, Janssen-Cilag, Leo, Eli Lilly and Company, Medac, Novartis, UCB Pharma, and has
participated as a consultant (honoraria) for Abbvie, Boehringer Ingelheim Pharma, Covagen, Forward Pharma,
Janssen-Cilag, Leo, Eli Lilly and Company, UCB Pharma, and Xenoport.
Prof. Reich has received funding for research/clinical studies (paid study fees to SCIderm GmbH) from Abbvie,
Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo,
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
Effect of bodyweight on ixekizumab treatment 1197
Eli Lilly and Company, Medac, Merck Sharp & Dohme Corp., Novartis, Regeneron, Takeda, and UCB Pharma. Dr.
Puig has received grants/research supports (clinical trials) from Abbvie, Amgen, Janssen, Eli Lilly and Company,
Novartis, Pfizer, Regeneron, and Roche, has received honoraria or consultation fees from Abbvie, Almirall,
Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, Leo-Pharma, Eli Lilly and Company,
Merck-Serono, MSD, Novartis, Pfizer, Regeneron, Roche, and Sandoz, and has participated in a company
sponsored speaker's bureau for Celgene, Janssen, Eli Lilly and Company, MSD, Novartis, and Pfizer.
Dr. Mallbris, Dr. Zhang, and Dr. Osuntokun are employees and stockholders of Eli Lilly and Company.
Dr. Leonardi is a Consultant/Advisory Board Member for Abbvie, Amgen, Boehringer-Ingelheim, Dermira, Eli Lilly
and Company, Janssen, Leo Pharmaceuticals, Pfizer, Sandoz, UCB and Vitae. He has been an investigator for
Actavis, Abbvie, Amgen, Boehringer-Ingelheim, Celgene, Coherus, Cellceutix, Corrona, Dermira, Eli Lilly and
Company, Galderma, Glenmark, Janssen, Leo Pharma, Merck, Novartis, Novella, Pfizer, Sandoz, Stiefel, Wyeth
and is on the speaker bureau for Abbvie, Celgene, Novartis and Eli Lilly and Company.
Funding sources
Funding for this research was provided by Eli Lilly and Company.
Clinicaltrials.gov
NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3).
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
1198 Reich et al.
Figure 1 Disposition of patients with moderate-to-severe plaque psoriasis enrolled in Phase 3 ixekizumab trials. Patients were randomly
assigned to one of four treatment groups: PBO, ETN, IXE Q4W or IXE Q2W. Disposition is shown by bodyweight category (<80 kg, 80 to
<100 kg, ≥100 kg) within each treatment group. ETN, etanercept; IXE Q4W, 80-mg ixekizumab every 4 weeks; IXE Q2W, 80-mg ixek-
izumab every 2 weeks; PBO, placebo.
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
Table 1 Baseline demographics and clinical characteristics
PBO ETN IXE Q4W IXE Q2W
N = 789 N = 739 N = 1159 N = 1168
<80 kg 80 to <100 kg ≥100 kg <80 kg 80 to <100 kg ≥100 kg <80 kg 80 to <100 kg ≥100 kg <80 kg 80 to <100 kg ≥100 kg
Bodyweight, n (%) 258 (33%) 280 (35%) 251 (32%) 234 (32%) 254 (34%) 251 (34%) 354 (31%) 437 (38%) 368 (32%) 394 (34%) 425 (36%) 349 (30%)
Age, years 45 14 47 13 46 12 44 15 47 13 46 12 44 14 46 13 46 12 44 14 46 13 46 12
Age, range 18–79 18–77 19–72 17–79 18–88 19–73 18–82 18–88 18–77 17–84 19–78 19–75
Extreme 0 4 (1%) 80 (32%) 0 0 90 (36%) 0 2 (<1%) 115 (31%) 0 3 (<1%) 113 (32%)
obese
Geographic
region, n (%)
Asia 11 (4%) 2 (<1%) 0 0 0 0 8 (2%) 3 (<1%) 1 (<1%) 7 (2%) 1 (<1%) 0
North America 110 (43%) 141 (50%) 152 (61%) 102 (44%) 127 (50%) 154 (61%) 167 (47%) 213 (49%) 221 (60%) 179 (45%) 206 (49%) 211 (61%)
Europe 123 (48%) 120 (43%) 90 (36%) 113 (48%) 111 (44%) 89 (36%) 156 (44%) 198 (45%) 133 (36%) 189 (48%) 199 (47%) 123 (35%)
Central/South 6 (2%) 6 (2%) 2 (<1%) 15 (6%) 11 (4%) 4 (2%) 14 (4%) 12 (3%) 3 (<1%) 16 (4%) 8 (2%) 5 (1%)
America
Australia 8 (3%) 11 (4%) 7 (3%) 4 (2%) 5 (2%) 4 (2%) 9 (3%) 11 (3%) 10 (3%) 3 (<1%) 11 (3%) 10 (3%)
Race, n (%)
Indigenous 1 (<1%) 2 (<1%) 1 (<1%) 0 2 (<1%) 2 (<1%)* 3 (<1%) 1 (<1%)* 2 (<1%) 1 (<1%) 2 (<1%)* 2 (<1%)
American†
Asian 21 (8%) 5 (2%) 8 (3%) 12 (5%) 7 (3%) 0 22 (6%) 15 (3%) 8 (2%) 26 (7%) 13 (3%) 3 (<1%)
Black/African 2 (<1%) 15 (5%) 9 (4%) 5 (2%) 9 (4%) 9 (4%) 10 (3%) 10 (2%) 10 (3%) 4 (1%) 4 (<1%) 10 (3%)
American
Native 1 (<1%) 0 0 0 0 2 (<1%) 0 0 3 (<1%) 2 (<1%) 0 2 (<1%)
Hawaiian/Pacific
Islander
White 233 (90%) 258 (92%) 232 (92%) 215 (92%) 234 (93%) 232 (93%) 316 (90%) 406 (93%) 344 (94%) 359 (91%) 403 (95%) 329 (94%)
Multiple races 0 0 1 (<1%) 1 (<1%) 1 (<1%) 4 (2%) 1 (<1%) 4 (<1%) 0 1 (<1%) 3 (<1%) 3 (<1%)
Hispanic/Latino 18 (7%) 21 (8%) 11 (4%) 27 (12%) 26 (10%) 25 (10%) 32 (9%) 41 (9%) 17 (5%) 39 (10%) 26 (6%) 28 (8%)
origin, n (%)
Duration of 20 12 19 12 19 12 19 13 18 12 18 12 19 12 19 12 19 12 18 12 19 12 19 12
psoriasis, years
Previous
systemic therapy
Never used 87 (34%) 110 (39%) 85 (34%) 80 (34%) 101 (40%) 112 (45%) 121 (34%) 145 (33%) 140 (38%) 133 (34%) 145 (34%) 125 (36%)
1199
BMI, body mass index; ETN, etanercept; IXE Q4W, ixekizumab dosing every 4 weeks; IXE Q2W, ixekizumab dosing every 2 weeks; PASI, Psoriasis Area and Severity Index; PBO, placebo; SD, standard
PASI 75
3.6 0.6*,***
<80 kg
20.7 7.5
121 (35%)
76 (22%)
88 (25%)
≥100 kg
27 (8%)
80 to 100 kg
≥100 kg
-20 -15 -10 -5 0 5 10 15 20
Favours
IXE Q4W IXE Q2W
80 to <100 kg
PASI 90
19.8 7.8
154 (36%)
107 (25%)
3.5 0.6
45 (11%)
81 (19%)
<80 kg
80 to 100 kg
≥100 kg
-20 -15 -10 -5 0 5 10 15 20
19.8 8.3
175 (44%)
Favours
3.5 0.6
N = 1168
IXE Q2W
88 (22%)
31 (8%)
**P ≤ 0.05 vs. ETN using CMH test stratified by study for categorical data and analysis of variance (ANOVA) for continuous data. UNCOVER-2 and UNCOVER-3 only.
<80 kg
PASI 100
<80 kg
80 to 100 kg
≥100 kg
21.3 7.5
120 (33%)
3.7 0.6
40 (11%)
68 (19%)
84 (23%)
≥100 kg
20.4 7.5
172 (39%)
3.5 0.6
43 (10%)
77 (18%)
99 (23%)
3.5 0.6
N = 1159
IXE Q4W
53 (15%)
82 (23%)
30 (9%)
<80 kg
29 (12%)
47 (19%)
≥100 kg
21 (8%)
3.5 0.6
49 (19%)
20 (8%)
23 (9%)
American Indian from North, Central and South America and Alaska Native.
24 (10%)
55 (24%)
N = 739
18 (8%)
<80 kg
31 (12%)
64 (26%)
70 (28%)
≥100 kg
28 (10%)
58 (21%)
68 (24%)
Results
20.4 8.7
3.5 0.6
96 (37%)
33 (13%)
42 (16%)
66 (26%)
N = 789
<80 kg
PBO
Patient disposition
Table 1 Continued
Biologic and
non-biologic
sPGA
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
Effect of bodyweight on ixekizumab treatment 1201
category for the IXE Q4W (N = 1159), IXE Q2W the IXE Q4W (<80 kg: 44.6%; 80 to <100 kg: 35.7%;
(N = 1168), PBO (N = 789) and ETN (N = 739) groups as ≥100 kg: 23.1%) and IXE Q2W group (<80 kg: 47.7%; 80 to
well as the number of completers and reasons for discontinu- <100 kg: 42.4%; ≥100 kg: 26.9%) relative to PBO (<80 kg:
ation are shown in Fig. 1. The distribution of patients in the 0%; 80 to <100 kg: 0.4%; ≥100 kg: 0%; P < 0.001 all com-
different bodyweight categories as well as the overall distribu- parisons) and ETN (<80 kg: 11.1%; 80 to <100 kg: 7.1%;
tion of baseline bodyweight were similar between treatment ≥100 kg: 4.0%; P < 0.05 all comparisons). Regardless of
groups. The number of completers and reasons for discontin- bodyweight, the percentage of patients achieving complete
uation were also consistent across treatment groups within skin clearance (sPGA 0) or nearly complete skin clearance
each bodyweight category (Table 1 and Fig. 1). (sPGA 0,1) was higher in the IXE Q2W than the IXE Q4W
group.
Baseline demographics and clinical characteristics Using a logistic regression model with baseline bodyweight
Baseline demographics and patients characteristics were gener- as a continuous covariate, significantly more patients in the
ally consistent across treatment groups within each bodyweight IXE Q4W and IXE Q2W treatment groups achieved PASI
category with a few exceptions (Table 1). In the 80- to <100-kg 75, PASI 90, PASI 100, sPGA (0,1) and sPGA (0) at Week
bodyweight category, there was significantly higher percentage 12 relative to PBO (P < 0.001 all comparisons) and ETN
of women of the IXE Q4W and IXE Q2W groups than in the (P < 0.001 all comparisons). The responses were higher with
PBO group as well as a significant difference in the distribution IXE Q2W than with IXE Q4W (P < 0.05 all comparisons)
of patients by race in the IXE Q2W group relative to PBO. In the at Week 12.
≥100-kg bodyweight category, there was a significantly lower
baseline sPGA score in the IXE Q2W group relative to IXE Q4W Efficacy by body mass index
and PBO. Across BMI categories, significantly more patients in the IXE
Q4W and IXE Q2W treatment groups achieved PASI 75,
Efficacy by bodyweight PASI 90 and PASI 100 relative to PBO (Table 3). Similarly,
At Week 12, across all bodyweight categories, the percentage of significantly more patients in the IXE Q4W and IXE Q2W
patients achieving PASI 75, PASI 90 or PASI 100 was higher in treatment groups achieved PASI 75, PASI 90 and PASI 100
the IXE Q2W group than in the IXE Q4W group (Fig. 2). relative to ETN across BMI categories except the lower
Across all bodyweight categories, significantly more patients weight category. Across all BMI categories, the percentage of
in the IXE Q4W and IXE Q2W treatment groups achieved PASI patients achieving sPGA 0,1 or sPGA 0 at Week 12 was also
75 by Week 1, PASI 90 by Week 2 and PASI 100 by Week 4 rela- significantly higher in the IXE Q4W and IXE Q2W groups
tive to PBO or ETN (Fig. 3). The percentage of patients achiev- than PBO (Table 3). Significantly more patients in the IXE
ing PASI 75, PASI 90 or PASI 100 continued to increase over the Q4W and IXE Q2W treatment groups achieved sPGA 0,1 or
12 weeks of treatment regardless of bodyweight category. sPGA 0 relative to ETN across BMI categories except the
Among ixekizumab-treated patients, at least 74% of patients in lower weight category. Similar to analyses by bodyweight cat-
each bodyweight category achieved PASI 75 at Week 12 (Fig. 3 egories, the responses by BMI categories were generally higher
and Table 2). While a numerically lower number of patients with IXE Q2W than with IXE Q4W.
achieved PASI 75, PASI 90 and PASI 100 with increasing body-
weight, both ixekizumab treatment groups demonstrated high Safety
efficacy across all bodyweight categories relative to PBO and In general, TEAEs, SAEs and AEs of special interest occurred at a
ETN. similar frequency for each treatment group (Table 4).
The individual percent improvement in PASI at Week 12 by Overall, the incidence of TEAEs was significantly higher in the
baseline bodyweight for each patient in the IXE Q2W group is IXE Q4W, IXE Q2W and ETN groups than in the PBO group
plotted in Fig. 4. (Table 4). The most frequently reported events (occurring in
Similarly, across all bodyweight categories, the percentage ≥5% of ixekizumab-treated patients per bodyweight category)
of patients achieving sPGA 0,1 at Week 12 was significantly were nasopharyngitis, upper respiratory tract infection and
higher in the IXE Q4W (<80 kg: 79.4%; 80 to <100 kg: injection-site reactions. Injection-site reaction was the only
78.7%; ≥100 kg: 67.4%) and IXE Q2W groups (<80 kg: TEAE that occurred at a statistically higher incidence in the
85.8%; 80 to <100 kg: 83.3%; ≥100 kg: 75.6%) than PBO active treatment groups (IXE Q4W, IXE Q2W and ETN) than in
(<80 kg: 5.4%; 80 to <100 kg: 4.3%; ≥100 kg: 2.0%; the PBO group. The percentage of patients who discontinued
P < 0.001 all comparisons) and ETN (<80 kg: 47.4%; 80 to due to AE was similar across bodyweight categories for all four
<100 kg: 42.1%; ≥100 kg: 27.9%; P < 0.001 all comparisons). groups (range: 0.4–2.8%).
The percentage of patients achieving sPGA 0 at Week 12 No deaths were reported during the 12-week treatment period
was also consistently higher across bodyweight categories in (Table 4). Across all bodyweight categories, SAEs occurred at a
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
1202 Reich et al.
Patients, %
†† **
**
††
60 60 ** 60 ††
**
40 †† 40 ††
40
**
** ††
20 † 20 † 20 †
**
** ** *
0 0 0
1 2 4 8 12 1 2 4 8 12 1 2 4 8 12
PASI 90 100 100 100
††
** ††
80 80 80
Patients, %
†† **
**
††
†† **
60 60 ** 60 ††
**
40 †† 40 40
** ††
** ††
20 †† 20 † 20 †
**
** **
*
0 0 0
1 2 4 8 12 1 2 4 8 12 1 2 4 8 12
60 ††
*
60 ††
60
††
*
40 * 40 40 ††
*
†† ††
††
20 *
20 †† * 20 † *
† *
*
**
0 0 0
1 2 4 8 12 1 2 4 8 12 1 2 4 8 12
Weeks Weeks Weeks
†† **
** ††
60 60 ** 60 ††
**
†
40 **
40 †† 40
††
** **
†
20 20 † 20 †
** ** *
0 0 0
1 2 4 8 12 1 2 4 8 12 0 2 4 6 8 10 12
80 80 ** 80 ††
** †† **
60 60 ** 60 ††
†† **
40 ** 40 †† 40
** ††
20 †† 20 †† 20 **
** †
** *
0 0 0
1 2 4 8 12 1 2 4 8 12 1 2 4 8 12
80 80 80
††
60 **
60 ††
60
†† **
40 ** 40 †† 40 ††
**
†† ** ††
20 **
20 †† 20 †
**
**
* **
0 0 0
1 2 4 8 12 1 2 4 8 12 1 2 4 8 12
Weeks Weeks Weeks
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
Effect of bodyweight on ixekizumab treatment 1203
CI, confidence interval; ETN, etanercept; IXE Q4W, ixekizumab dosing every 4 weeks; IXE Q2W, ixekizumab dosing every 2 weeks; PASI, Psoriasis Area and Severity Index; PBO, placebo, sPGA, static
Figure 3 (a) PASI 75, PASI 90 and PASI 100 response rates over
299 (85.7%)*,**,***
210 (60.2%)*,**
12 weeks of treatment across bodyweight categories for patients
90 (25.8%)*,**
treated with PBO, ETN or IXE Q2W. *P ≤ 0.05, Q2W vs. PBO,
[82.0, 89.3]
[55.0, 65.3]
[21.2, 30.4]
≥100 kg
CMH test stratified by study. **P ≤ 0.001, Q2W vs. PBO, CMH
test stratified by study. †P ≤ 0.05, Q2W vs. ETN, CMH test strati-
349
fied by study. ††P ≤ 0.05, Q2W vs. ETN, CMH test stratified by
380 (89.4%)*,**
300 (70.6%)*,**
166 (39.1%)*,**
study. Comparisons with ETN included patients enrolled in
80 to <100 kg
UNCOVER-2 and UNCOVER-3 only. (b) PASI 75, PASI 90 and
[86.5, 92.3]
[66.3, 74.9]
[34.4, 43.7]
PASI 100 response rates over 12 weeks of treatment across body-
weight categories for patients treated with IXE Q2W or IXE Q4W.
425
*P ≤ 0.05, Q4W vs. PBO, CMH test stratified by study.
**P ≤ 0.001, Q4W vs. PBO, CMH test stratified by study.
358 (90.9%)*,**,***
†
P ≤ 0.05, Q4W vs. ETN, CMH test stratified by study. ††P ≤ 0.05,
184 (46.7%)*,**
307 [77.9%)*,**
[88.0, 93.7]
[73.8, 82.0]
[41.8, 51.6]
Q4W vs. ETN, CMH test stratified by study. Comparisons with ETN
N = 1168
IXE Q2W
<80 kg
included patients enrolled in UNCOVER-2 and UNCOVER-3 only.
#
P ≤ 0.05, Q4W vs. Q2W, CMH test stratified by study.
394
##
P ≤ 0.001, Q4W vs. Q2W, CMH test stratified by study. ETN,
273 (74.2%)*,**
194 (52.7%)*,**
etanercept; IXE Q4W, 80-mg ixekizumab every 4 weeks; IXE Q2W,
81 (22.0%)*,**
80-mg ixekizumab every 2 weeks; PASI, Psoriasis Area and Sever-
[69.7, 78.7]
[47.6, 57.8]
[17.8, 26.2]
≥100 kg
ity Index; PBO, placebo.
368
374 (85.6%)*,**
286 (65.4%)*,**
150 (34.3%)*,**
80 to <100 kg
[82.3, 88.9]
[61.0, 69.9]
[29.9, 38.8]
similar frequency for each treatment group (range: 1.3–2.6%).
437
Four SAEs were reported in more than one patient per body-
weight category: cellulitis (<80 kg PBO, n = 1; ≥100 kg ETN,
303 (85.6%)*,**
257 (72.6%)*,**
155 (43.8%)*,**
n = 1; <80 kg IXE Q4W, n = 2, P < 0.05 vs. PBO; ≥100 kg IXE
[81.9, 89.3]
[68.0, 77.2]
[38.6, 49.0]
Q2W, n = 1), appendicitis (80 to <100 kg IXE Q2W, n = 2),
N = 1159
IXE Q4W
<80 kg
29 (11.6%)*
[31.1, 43.0]
[7.6, 15.5]
9 (3.6%)*
[1.3, 5.9]
≥100 kg
**P ≤ 0.001 vs. ETN using CMH test stratified by study; UNCOVER-2 and UNCOVER-3 only.
The most frequently reported infections, nasopharyngitis
251
123 (48.4%)*
64 (25.2%)*
[42.3, 54.6]
[19.9, 30.5]
254
72 (30.8%)*
[52.2, 64.9]
[24.9, 36.7]
23 (9.8%)*
<80 kg
234
[vs. ETN (0.4%, n = 1), P < 0.05]. The five remaining cases
*P ≤ 0.05 vs. PBO using CMH test stratified by study.
8 (3.2%)
<100 kg IXE Q4W, ≥100 IXE Q4W, <80 kg IXE Q2W and
80 to <100 kg
[0.2, 3.3]
5 (1.8%)
1 (0.4%)
[0, 1.1]
<80 kg
[0, 3.1]
PBO
[95% CI]
[95% CI]
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
1204 Reich et al.
n = 51 n = 80 n = 89
40 (4.5%) (7.1%) (7.9%)
30
20
10 n = 90
0
-10
-20
-30
n = 23 n = 26 n = 41
-40
(2.0%) (2.3%) (3.6%)
-50
-60
40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200
Weight (kg)
Figure 4 Scatterplot of PASI percent improvement at Week 12 by baseline bodyweight for the IXE Q2W treatment group (observed data;
integrated from UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies; N = 1127). IXE Q2W, 80-mg ixekizumab every 2 weeks; PASI 75,
75% improvement from baseline on the Psoriasis Area and Severity Index; PASI 90, 90% improvement from baseline on the Psoriasis
Area and Severity Index.
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
Effect of bodyweight on ixekizumab treatment 1205
*P ≤ 0.05 vs. PBO, CMH test stratified by study. Comparisons with ETN included patients enrolled in UNCOVER-2 and UNCOVER-3 only.
**P ≤ 0.05 vs. ETN, CMH test stratified by study. Comparisons with ETN included patients enrolled in UNCOVER-2 and UNCOVER-3 only.
BMI categories were underweight <18.5 kg/m2; normal ≥18.5 to <25 kg/m2; overweight ≥25 to <30 kg/m2; obese ≥30 to <40 kg/m2; and extreme obese
≥40 kg/m2.
BMI, body mass index; ETN, etanercept; IXE Q4W, ixekizumab dosing every 4 weeks; IXE Q2W, ixekizumab dosing every 2 weeks; PASI, Psoriasis Area
and Severity Index; PBO, placebo; sPGA, static Physician’s Global Assessment.
JEADV 2017, 31, 1196–1207 © 2017 European Academy of Dermatology and Venereology
1206
*P ≤ 0.05 vs. PBO, CMH test stratified by study. Comparisons with ETN included patients enrolled in UNCOVER-2 and UNCOVER-3 only.
**P ≤ 0.05 vs. ETN, CMH test stratified by study. Comparisons with ETN included patients enrolled in UNCOVER-2 and UNCOVER-3 only.
†
Five patients in the IXE Q2W group in the 80 to <100 kg bodyweight category experienced oral candidiasis in UNCOVER-2 and UNCOVER-3. One additional from UNCOVER-1 also experienced oral
candidiasis.
‡
≥5% of patients in each ixekizumab-treated bodyweight category.
AE, adverse event; ETN, etanercept; IXE Q4W, ixekizumab dosing every 4 weeks; IXE Q2W, ixekizumab dosing every 2 weeks; PBO, placebo; SAEs, serious adverse events; TE, treatment-emergent,
URT, upper respiratory tract.
Reich et al.
Acknowledgements 3 Puig L. Obesity and psoriasis: body weight and body mass index influence
the response to biological treatment. J Eur Acad Dermatol Venereol 2011;
The authors would like to acknowledge Janelle Erickson of Eli
25: 1007–1011.
Lilly and Company (Indianapolis, IN) for her thorough review 4 Liu L, Lu J, Allan BW et al. Generation and characterization of ixek-
and input on the manuscript and would also like to acknowledge izumab, a humanized monoclonal antibody that neutralizes interleukin-
Kelly Guerrettaz, inVentiv Health Clinical (Princeton, NJ), for 17A. J Inflamm Res 2016; 9: 39–50.
5 Gordon KB, Blauvelt A, Papp KA et al. Phase 3 trials of ixekizumab
her assistance with manuscript writing.
in moderate-to-severe plaque psoriasis. N Engl J Med 2016; 375: 345–
356.
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