Background/Purpose:

Enthesitis-related
arthritis (ERA) is a juvenile idiopathic arthritis (JIA) category affecting
entheses and joints. The REMINDER study to analyse the efficacy of etanercept (ETA)
in active and refractory ERA pts, was used to analyse the stability of remission
on and off medication (Horneff et al. Arthritis
Rheumatol. 2015 Apr 17).

Methods:

In this 2-part, 48-week,
randomised, placebo-controlled, double-blind withdrawal study, first, all pts
received open-label ETA for 24 weeks. At week 24, pts with at least a JIA-ACR30
response entered a 24-week randomised (1:1 placebo (PLC) or ETA), double-blind
withdrawal period. Remission was defined as JADAS10≤1.0. In addition,
absence of tender enthesis (TE), active uveitis and spinal involvement (judged
by BASDAI) were analysed.

Results:

41 pts (mean age 13.4 y, disease duration 2.8 y, active joint count
5.3, JADAS10 15.8) received open-label ETA (0.8 mg/kg bw., max.50 mg/week) for
24 weeks. 2 pts discontinued prematurely, one for intolerance and one due to a
protocol violation. JIA-ACR30/50/70/90/100 response rates at week 24 were 93%/93%/80%/56%
and 54%. Remission (JADAS) was reached by 14.6/35/51.3/59.0% at week
4/12/16/24. Until Week 48, 9 JIA-ACR30 flares occurred on PLC, 3 on ETA (odds
ratio 6.0, p = 0.02). Until week 48, 6 of 11 (55%) pts had stable JADAS
remission while continuing on ETA and 3 of 12 (25%) on PLC (OR 3.6 [0.6-21,
p=0.15). An additional patient randomized to ETA achieved remission at week 28
and stayed in remission until week 48. Two pts of the ETA cohort had a disease
reactivation at week 28 and week 32, which did not qualify for an ACR30 flare.
They continued on double blind ETA and regained remission thereafter. The mean
TE count decreased from 1.8 [range 0-7] to 0.8, 0.4, 0.2 and 0.5 and the rate
of pts with no TE increased from 34% to 79/76/84/84% at week 4/8/12/24. 13/17 (76%)
pts on ETA with no TE at week 24 remained without TE until week 48. 9 pts (69%)
of the PLC cohort continued without a TE from week 24 to 48. The mean BASDAI
score decreased from 2.6 (range 0-7.3) to 0.8/0.7/0.5/0.4 and the number of pts
with a BASDAI of 0 increased from 7.8% to 31.5/34.2/36.8/50% at week 4/8/16/24.
7/10 pts on ETA with BASDAI of 0 at week 24 remained with a BASDAI of 0 until
week 48. All 7 pts randomized to placebo, who had a BASDAI of 0 maintained a
BASDAI of 0 until week 48 or until reset on ETA. A single uveitis event was
reported in a patient randomized to ETA at week 48.

Conclusion: In this placebo-controlled
randomized trial ETA proved to be effective with a high rate of pts reaching
JADAS remission. Remission continued off treatment in a quarter of pts only
while more pts remain in stable remission who continued treatment with ETA.

Figure 1 Kaplan Meyer curve showing stability of remission on PLC
(red) and ETA (blue). Hazard ratio 2.20 [0.66-7.36], p=0.16