A total of 455 patients were included in this analysis, of whom 177 (38.9%) patients received IXE monotherapy (ie, with no concomitant cDMARDs) for up to a year of treatment. Of the 230 (50.5%) patients who received MTX at some point through Week 52, 183 (40.2%) patients received IXE with a stable dose of concomitant MTX up to Week 52. Forty-eight (10.5%) patients received cDMARDs other than MTX and were not included in this analysis.
The number of patients (n=47) undergoing MTX dose tapering/modification up to Week 52 included the following: 5 (1.1%) increased MTX dosing, 8 (1.8%) added MTX to their IXE therapy, 9 (2.0%) discontinued MTX therapy and restarted it later (at a higher or lower dose), 14 (3.1%) tapered their MTX dosing, 9 (2.0%) discontinued MTX therapy by Week 52, and 2 (<1%) had missing data. Generally, a similar proportion of patients modified the MTX use between the treatment regimens; however, more patients in the IXE Q2W group tapered while more patients in the IXE Q4W group discontinued MTX.
Patient demographics and baseline characteristics were similar across IXE Q4W or Q2W monotherapy versus concomitant MTX groups (Table 1). The stable average dosing of MTX for the IXE Q4W group was 15.7 mg/week and for the IXE Q2W group was 16.0 mg/week (Table 2).
Table 1. Baseline Demographics and Disease Characteristics
|
SPIRIT-P1 and SPIRIT-P2
|
IXE Q4W
|
IXE Q2W
|
No MTX/ cDMARDs (N=95)
|
MTXa
(N=85)
|
No MTX/ cDMARDs (N=82)
|
MTXa
(N=98)
|
Age, years
|
51.2 (12.3)
|
52.0 (12.4)
|
52.0 (12.0)
|
49.1 (11.7)
|
Male, n (%)
|
46 (48.4)
|
41 (48.2)
|
38 (46.3)
|
44 (44.9)
|
Weight, kg
|
87.0 (22.6)
|
87.2 (18.1)
|
85.0 (21.9)
|
83.3 (18.1)
|
Time since PsA diagnosis, years
|
10.5 (9.6)
|
6.5 (6.6)
|
9.2 (9.0)
|
8.6 (7.0)
|
Patients with specific disease characteristics, n (%)
|
Enthesitisb
|
53 (55.8)
|
50 (58.8)
|
53 (65.4)^
|
58 (59.8)f
|
Dactylitisc
|
26 (27.4)
|
22 (25.9)
|
16 (19.5)
|
23 (23.7)f
|
Current psoriasisd
|
93 (97.9)
|
80 (94.1)
|
77 (93.9)
|
91 (92.9)^^
|
Baseline disease and quality of life scores
|
TJC (68 joints)
|
21.8 (13.6)
|
20.6 (15.1)
|
25.2 (16.6)
|
21.7 (15.1)
|
SJC (66 joints)
|
12.4 (8.9)
|
11.7 (10.8)
|
13.7 (10.0)
|
11.9 (8.1)
|
PGA VAS
|
60.1 (19.3)
|
57.9 (20.6)
|
62.9 (19.1)
|
61.9 (16.4)
|
PatGA VAS
|
66.5 (18.8)
|
64.0 (22.0)
|
64.9 (21.4)
|
63.8 (20.6)
|
Patients assessment of Pain VAS
|
63.0 (20.1)
|
63.0 (21.6)
|
61.5 (21.5)
|
62.1 (21.7)
|
HAQ-DI
|
1.2 (0.6)
|
1.2 (0.6)
|
1.2 (0.6)
|
1.2 (0.6)
|
hsCRP, mg/L
|
16.6 (27.0)
|
15.2 (21.6)
|
15.6 (29.3)
|
14.1 (22.8)
|
PASI
|
7.5 (8.6)
|
6.3 (6.4)
|
6.9 (7.9)
|
6.0 (8.6)
|
% BSAe
|
13.9 (18.8)
|
14.9 (16.0)
|
10.6 (14.7)
|
13.1 (19.6)
|
Data are mean (standard deviation) unless stated otherwise.
aPatients with stable dose of MTX from Weeks 0 to 52 only.
bBaseline enthesitis defined as a baseline LEI score >0.
cBaseline dactylitis defined as a baseline LDI-B score >0.
dCurrent psoriasis as assessed by physician.
ePatients with psoriasis at baseline.
fThe number of patients evaluated was N=97
^Number of patients evaluated in this group was 81.
^^Number of patients evaluated in this group was 98.
Abbreviations: BSA=body surface area involvement; cDMARD=conventional disease-modifying antirheumatic drug; HAQ-DI=Health Assessment Questionnaire-Disability Index; hsCRP=high sensitivity C-reactive protein; IXE Q2W=80 mg ixekizumab every 2 weeks; IXE Q4W=80 mg ixekizumab every 4 weeks; LDI-B=Leeds Dactylitis Index-Basic; LEI=Leeds Enthesitis Index; MTX=methotrexate; N=number of patients in each group; n=number of patients in specific group; PASI=Psoriasis Area and Severity Index; PatGA=Patient’s Global Assessment of Disease Activity; PGA=Physician’s Global Assessment of Disease Activity; PsA=psoriatic arthritis; SJC=swollen joint count; TJC=tender joint count; VAS=visual analog scale.
Table 2. Summary of MTX use between Weeks 0 and 52 in patients with stable MTX dose
|
SPIRIT-P1 and SPIRIT-P2
|
|
IXE Q4W
(N=229)
|
IXE Q2W
(N=226)
|
Patients with stable MTX dose, n (%)
|
85 (37.1)
|
98 (43.4)
|
Overall average dose, mg/week
|
15.7
|
16.0
|
Route of MTX administration:
|
Intramuscular, n (%)
|
1 (1.2)
|
2 (2.0)
|
Average dose, mg/week
|
25.0
|
12.5
|
Subcutaneous, n (%)
|
14 (16.5)
|
15 (15.3)
|
Average dose, mg/week
|
17.7
|
19.7
|
Oral, n (%)
|
70 (82.4)
|
81 (82.7)
|
Average dose, mg/week
|
15.2
|
15.4
|
Abbreviations: IXE Q2W=80 mg ixekizumab every 2 weeks; IXE Q4W=80 mg ixekizumab every 4 weeks; MTX=methotrexate; N=number of patients in each group; n=number of patients in specific group.
Generally, ACR20/50/70 responses were similar or higher in patients receiving IXE Q4W or Q2W monotherapy compared with those receiving stable dose concomitant MTX during the double-blind treatment period (up to Week 24). Although not formally tested for comparison from Week 36 onward, the proportion of patients achieving ACR responses was higher in patients receiving IXE Q4W or Q2W monotherapy compared with those receiving stable dose concomitant MTX (Figure 1). At Week 52, the ACR20/50/70 response rates in IXE Q4W monotherapy and stable dose concomitant MTX groups were 66.3% and 55.3%, 48.4% and 38.8%, and 35.8% and 27.1%, respectively. Similar responses were seen for IXE Q2W monotherapy compared with stable dose concomitant MTX groups (Figure 1). In patients randomized to IXE and receiving MTX at baseline irrespective of subsequent dose change, there was no apparent increase in the percentage of patients achieving ACR20/50/70 responses at Week 52 relative to patients receiving IXE as monotherapy. At Week 52, in IXE Q4W and Q2W treatment arms in patients with concomitant MTX use at baseline, the response rates for ACR20/50/70 were 56.1% (both groups), 40.2% and 38.6%, and 26.2% and 23.7%, respectively (Figure S2 (Additional File 1)).
Week 52 change from baseline in TJC and SJC for patients with IXE monotherapy and those receiving stable dose concomitant MTX are presented in Table S1.
At Week 52, the DAPSA LDA response rates in IXE Q4W monotherapy versus stable dose concomitant MTX groups were 52.6% versus 52.9%, respectively, whereas, the DAPSA LDA response rates in IXE Q2W monotherapy versus stable dose concomitant MTX groups were 54.9% versus 40.8%, respectively. Overall, the proportion of patients achieving disease control (as measured by DAPSA LDA or MDA was similar in patients receiving IXE Q4W/Q2W monotherapy relative to patients receiving concomitant stable dose MTX therapy up to Week 52 (Figure 2). Although not formally tested for comparison, the proportion of patients achieving MDA or DAPSA LDA was higher in those receiving IXE Q2W monotherapy compared with those receiving IXE Q2W and stable dose concomitant MTX.
Throughout 52 weeks of treatment, the proportion of patients reporting TEAEs was similar between IXE Q4W groups with or without MTX. A higher proportion of patients who received IXE Q2W alone experienced TEAEs compared to those receiving concomitant MTX; however, TEAEs in general were rated mild or moderate in severity. Adverse events leading to discontinuation and SAEs were generally similar in either dosing regimen with or without MTX. Adverse events of special interest including injection site reactions, infection, and hepatic event were generally similar in both dosing regimens of IXE with or without MTX (Table 3).
Table 3: Safety overview of IXE with or without concomitant MTX after 52 weeks of treatment
|
SPIRIT-P1 and SPIRIT-P2
|
IXE Q4W (N=229)
|
IXE Q2W (N=226)
|
No MTX/ cDMARDs (N=95)
|
MTXa
(N=85)
|
No MTX/ cDMARDs (N=82)
|
MTXa
(N=97)
|
TEAEs (≥1)
|
75 (78.9%)
|
67 (78.8%)
|
71 (86.6%)
|
77 (79.4%)
|
Mild
|
31 (32.6%)
|
39 (45.9%)
|
32 (39.0%)
|
35 (36.1%)
|
Moderate
|
39 (41.1%)
|
24 (28.2%)
|
32 (39.0%)
|
35 (36.1%)
|
Severe
|
5 (5.3%)
|
4 (4.7%)
|
7 (8.5%)
|
7 (7.2%)
|
SAEs
|
6 (6.3%)
|
5 (5.9%)
|
4 (4.9%)
|
3 (3.1%)
|
Discontinuations due to AE
|
5 (5.3%)
|
2 (2.4%)
|
6 (7.3%)
|
9 (9.3%)
|
AEs of special interest
|
Cytopenias
|
1 (1.1%)
|
3 (3.5%)
|
3 (3.7%)
|
1 (1.0%)
|
Hepatic events
|
6 (6.3%)
|
2 (2.4%)
|
3 (3.7%)
|
9 (9.3%)
|
Infections
|
50 (52.6%)
|
37 (43.5%)
|
41 (50.0%)
|
47 (48.5%)
|
Injection-site reactions
|
20 (21.1%)
|
14 (16.5%)
|
23 (28.0%)
|
26 (26.8%)
|
Allergic reactions/hypersensitivities
|
8 (8.4%)
|
4 (4.7%)
|
8 (9.8%)
|
7 (7.2%)
|
Non-anaphylaxis
|
8 (8.4%)
|
4 (4.7%)
|
8 (9.8%)
|
7 (7.2%)
|
Malignancies
|
2 (2.1%)
|
0
|
0
|
0
|
Depression
|
2 (2.1%)
|
4 (4.7%)
|
2 (2.4%)
|
2 (2.1%)
|
Data presented are n (%).
Note: There were no cases of anaphylaxis, cerebro-cardiovascular events, MACE, ILD, IBD, CD, and UC observed in these subpopulations.aPatients with stable dose of MTX from Weeks 0 to 52 only.
Abbreviations: AEs=adverse events; CD=Crohn's disease; cDMARD=conventional disease-modifying antirheumatic drug; IBD=inflammatory bowel disease; ILD=interstitial lung disease; IXE Q2W=80 mg ixekizumab every 2 weeks; IXE Q4W=80 mg ixekizumab every 4 weeks; MACE=major adverse cerebro-cardiovascular events; MTX=methotrexate; N=number of patients in each group; n=number of patients; SAEs= serious adverse events; TEAEs=treatment-emergent adverse events; UC=ulcerative colitis.
Treatment-emergent AEs of diarrhea, nausea, and headache were reported similarly between patients receiving IXE dosing with or without MTX. Treatment-emergent abnormalities in laboratory values of whole blood neutrophils, platelets, and leukocytes as well as aspartate and alanine aminotransferase levels were similar or had no elevation between patients receiving IXE dosing with or without MTX (data not shown).