Session Information
Date: Tuesday, November 15, 2016
Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects II: Juvenile Arthritis
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: The data of the REMINDER study, a two-part, 48-week, randomized, placebo-controlled, double-blind withdrawal study on efficacy of etanercept (ETA) compared to placebo (PLC) in ERA patients is used to analyze the improvement of spinal symptoms (1).
Methods: Patients with active ERA received open-label ETA for 24 weeks. At week 24, patients with at least a JIA-ACR30 response entered a 24-week randomized (1:1 PLC or ETA), double-blind withdrawal period. Improvement was assessed by the number of active joints, the JIAACR30/50/70/90 and ACR remission criteria, the JADAS10, JADAS MDA and JADAS remission, the tender enthesitis points (TEP), and parameters of spinal involvement (BASDAI, BASFI and spinal pain (by VAS)).
Results: Forty-one patients (means for age: 13.4 years, baseline disease duration: 2.8 years, active joints count: 5.3, JADAS10: 15.8) were included and 39 received open-label ETA (0.8 mg/kg/week, max.50 mg/week) for 24 weeks. Two patients discontinued prematurely. Marked improvement was reached at week 24, the JIAACR30/50/70/90 response rates were 93%/93%/80%/56%. %. ACR remission was achieved by 23 patients (60.5%), respectively. JADAS MDA/remission was reached by 34 (87.1%)/23(60.5%) patients. The mean number of active joints decreased from 5.2+/-2.3 to 0.3+/-0.8. The mean BASDAI score decreased from 4.4+/-1.9 to 1.2+/-1.6 and the number of patients with a BASDAI of 0 increased from 0 to 26.3% (n=10). The mean BASFI improved from 2.7+/-2.4 to 0.36+/-0.68. 31(81.6%) of patients achieved an ASAS20 and 28 (73.7%) an ASAS40. Mean total spinal pain/spinal paint night also decreased from 5.2/2.9 to 1.5/0.5. The mean TEP count decreased from 1.8 [range 0-7] to 0.4 and the rate of patients with no tender enthesitis point more than doubled from 31.7% to 68.4%. Efficacy indicators were stable in patients receiving ETA in the double blind phase of the study, and worsened in part of the patients on PLC. Until week 48, 7/10 patients on ETA with BASDAI of 0 at week 24 remained with a BASDAI of 0. In all 3 cases with a JIA ACR30 flare, an increase of the BASDAI was noted (from 0 to 0.6, 1.1 and 7.6). All 7 patients randomized to placebo with a BASDAI of 0 at week 24 maintained a BASDAI of 0 until week 48 or until reset on ETA. Also 13/17 (76%) patients on ETA and 9 (69%) on PLC with no TEP at week 24 remained without TEP until week 48. A single uveitis event was reported in a patient randomized ETA at week 48.
Conclusion: In this placebo-controlled randomized study on ERA-JIA patients, ETA proved to be highly effective on peripheral disease as well as on spinal inflammation. A high rate of patients achieved JADAS remission, BASDAI 50, BASFI50, no spinal pain and no tender enthesitis points after 24 weeks of treatment. The study was underpowered to demonstrate differences between ETA and PLC cohort at week 48. (1) Horneff et al. Arthritis Rheumatol. 2015 Apr 17. doi: 10.1002/art.39145
|
Baseline |
ETAw24 |
P |
OR[95%CI) |
ETAw48 |
PLCw48 |
|
| Active joints (0-71), mean |
5.2+/-2.3 |
0.3+/-0.8 |
<0.001 |
0.8+/-1.2 |
1.2+/-1.5 |
|
| No active joint, n(%) |
0 |
31 (79.5%) |
<0.0001 |
181[21-1553) |
12 (60%) |
9 (50%) |
| JADAS10 (0-40), mean |
17.5+/-7.2 |
2.0+/-2.9 |
<0.001 |
3.3+/-4.3 |
4.4+/-5.3 |
|
| JADAS MDA, n(%) |
2(4.9%) |
34 (87.1) |
<0.0001 |
165[28-962] |
12 (60%) |
9(50%) |
| JASDAS Rem, n(%) |
0 |
23 (59%) |
<0.0001 |
62[8-507] |
11 (55%) |
9(50%) |
| ACR30,n(%) |
na |
38 (97.4%) |
19 (95%) |
16 (88.9%) |
||
| ACR50,n(%) |
na |
38 (97.4%) |
18 (90%) |
14 (77.8%) |
||
| ACR70,n(%) |
na |
33 (84.6%) |
13 (65%) |
9 (50%) |
||
| ACR90,n(%) |
na |
23 (59%) |
11 (55%) |
8 (44%) |
||
| ACRRem,n(%) |
0 |
23 (59%) |
<0.0001 |
62[8-507] |
11 (55%) |
6 (33%) |
| ASAS20,n(%) |
na |
31 (79.5%) |
12(60%) |
13(72%) |
||
| ASAS40,n(%) |
na |
28 (71.8%) |
11(55%) |
12(66%) |
||
| BASDAI(0-10), mean |
4.4+/-1.9 |
1.2+/-1.6 |
<0.001 |
1.6+/-2.1 |
1.5+/-1.6 |
|
| BASDAI50, mean |
n.a. |
28 (71.8%) |
15 (75%) |
13 (72.2%) |
||
| BASDAI=0,n(%) |
0 |
10 (25.%) |
0.002 |
14.6[1.8-120] |
7 (35%) |
6 (33%) |
| BASFI(0-10), mean |
2.7+/-2.4 |
0,36+/-0,68 |
<0.l001 |
0.78+/-1.7 |
0.67+/-1.2 |
|
| BASFI=0,n(%) |
3 (7.3%) |
19 (48.7%) |
<0,0001 |
12.6[3.3-48] |
11 (55%) |
6 (33%) |
| BASFI 50,n(%) |
n.a. |
34 (87.2) |
17 (85%) |
12 (66.7%) |
||
| Spinal pain (VAS 0-10), mean |
5.2+/-2.5 |
1.5+/-2.1 |
<0.001 |
2.3+/-3.1 |
1.7+/-1.2 |
|
| No Spinal pain, n(%) |
2 (4.9%) |
21 (53.8%) |
<0.0001 |
24.1[5.1-114] |
8 (40%) |
8 (44.4%) |
| Spinal pain night (0-10) , mean |
2.9+/-2.8 |
0.5+/-1.2 |
<0.001 |
1+/-2 |
1+/-1.7 |
|
| No Spinal pain, n(%) |
12 (29%) |
29 (74.4%) |
<0.0001 |
7.8[2.8-21] |
14 (70%) |
11 (61.1%) |
| Enthesitis-Points, mean |
1.8+/-1.9 |
0.4+/-1.3 |
<0.001 |
1.6+/-4.2 |
0,2+/-0.55 |
|
| No Enthesitis points, n(%) |
13 (31.7%) |
26 (66.7%) |
0.001 |
4.7[1.8-12.0] |
16 (80%) |
15 (83%) |
Table1: Disease activity parameters
To cite this abstract in AMA style:
Horneff G, Foeldvari I, Minden K, Huppertz HI, Klein A. Improvement of Spinal Inflammation Induced By Etanercept in Enthesitis Related Arthritis JIA-Patients. Data of the Reminder-Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/improvement-of-spinal-inflammation-induced-by-etanercept-in-enthesitis-related-arthritis-jia-patients-data-of-the-reminder-study/. Accessed .ACR Meeting Abstracts - https://acrabstracts.org/abstract/improvement-of-spinal-inflammation-induced-by-etanercept-in-enthesitis-related-arthritis-jia-patients-data-of-the-reminder-study/