基线MRI与CRP是依那西普对nr-axSpA的疗效预测因素

基线MRI与CRP是依那西普对nr-axSpA的疗效预测因素

EULAR2015; PresentID:
SAT0258

BASELINE MRI/CRP AS PREDICTORS OF RESPONSE
TO ETANERCEPT IN THE MANAGEMENT OF PATIENTS WITH NON-RADIOGRAPHIC
AXIAL SPONDYLOARTHRITIS

M.
A. Brown^1,*, P.
A. Bird¹, P.
C. Robinson²,
P. Mease³, F. van den
Bosch⁴, C. Surian⁵,
Z. Wiid⁵,
H. Jones⁶,
A. Szumski⁶,
L. Marshall⁶

¹Diamantina Institute, University of
Queensland, ²University of Queensland
& Royal Brisbane and Women's Hospital, Brisbane,
Australia,³Swedish Medical Center and University of
Washington, Seattle, United
States, ⁴Ghent University Hospital,
Ghent, Belgium, ⁵Pfizer Australia,
Sydney, Australia, ⁶Pfizer Inc,
Collegeville, United States

Background: Treatment
with TNFα inhibitors has been shown to be effective in improving
disease activity and functional capacity in patients with
non-radiographic axial spondyloarthritis
(nr-axSpA).  Evidence indicates that clinical
response to anti-TNFα agents tends to be enhanced in nr-axSpA
patients with magnetic resonance imaging (MRI)-documented
sacroiliac (SI) joint inflammation and elevated C-reactive protein
(CRP).

Objectives: To
determine if MRI sacroiliitis positivity and/or elevated CRP at
baseline are predictive or associated with changes in measures of
disease activity following etanercept (ETN) treatment in patients
with nr-axSpA.

Methods: Patients
with symptom duration >3
mths–<5 yrs, meeting ASAS axSpA classification criteria but not
radiographic criteria for ankylosing spondylitis, having BASDAI ≥4,
and failure with ≥2 NSAIDs were randomized to 12
wks of double-blind treatment with ETN 50mg QW or
PBO. Both groups continued stable NSAID therapy. Standard clinical
outcomes were assessed in 4 patient subgroups
based on MRI sacroiliitis (positive/negative [+/-]) and CRP
(elevated/normal [+/-]) status at baseline. MRI sacroiliitis
positivity was defined as SPARCC SI joint score ≥2; elevated CRP
was defined as >3 mg/L.

Results: A
total of 200 subjects (ETN, n=95; PBO, n=105) were included in
these analyses. At baseline, breakdown according to MRI
sacroiliitis and CRP status was: MRI-/CRP-, n=38; MRI+/CRP-, n=74;
MRI-/CRP+, n=21; MRI+/CRP+,
n=67. At Week 12, the primary
endpoint of ASAS40 was achieved by more patients receiving ETN than
those receiving PBO irrespective of MRI/CRP status at baseline
(Table). The greatest ASAS40
response was observed in patients with MRI+/CRP+ at baseline and
the lowest response was seen in the MRI-/CRP-
subgroup. Similar observations
were made for all other clinical endpoints with a markedly higher
proportion of MRI+/CRP+ patients achieving ASAS20, BASDAI50 and
clinically important improvements (Δ≥1.1) in ASDAS-CRP/ESR than
those in the other MRI/CRP subgroups.

Conclusions: Our
findings, in patients with early, active nr-axSpA and an inadequate
response to ≥2 NSAIDs, are consistent with the hypothesis that a
combination of MRI positivity and elevated hsCRP at baseline has a
positive predictive value on the SI joint inflammation score and a
better clinical response
to ETN. A larger sample size is
required to test this definitively.

背景：TNF拮抗剂已被证实可以有效改善nr-axSpA患者的疾病活动和功能。有证据表明，对于有MRI骶髂关节炎和CRP升高的患者，TNF拮抗剂的临床治疗反应率会增加。

目的：探讨nr-axSpA患者基线时存在MRI骶髂关节炎和/或升高的CRP是否对依那西普疗效有预测作用，或者与治疗后疾病活动度改善有相关性。

方法：病程大于3个月且小于5年、符合ASAS
axSpA分类标准但不符合强直性脊柱炎放射学标准、BASDAI≥4并且使用2种及以上NSAIDs治疗失败的患者被随机分组接受依那西普50mg/周或安慰剂的双盲治疗12周。期间,
两组都继续使用NSAIDs药物。根据基线时患者是否有MRI骶髂关节炎（+/-）和CRP的水平（高/正常）将患者分为4组进行临床疗效的分析。SPARCC
骶髂关节评分≥2分定义为MRI下骶髂关节炎阳性，CRP>3mg/L定义为CRP升高。

结果：共纳入200例患者（依那西普组95例，安慰剂组105例）。基线时，MRI骶髂关节炎与CRP水平如下：38例MRI-/CRP-，74例MRI+/CRP-，21例MRI-/CRP+，67例MRI+/CRP+。在12周时，无论基线时MRI及CRP的情况如何，接受依那西普治疗的患者ASAS40的反应率高于安慰剂组（参见表）。基线时MRI+/CRP+的患者接受依那西普治疗后ASAS40达标率最高，而基线时MRI-/CRP-的患者接受依那西普治疗后ASAS40达标率最低。ASAS20、BASDAI50以及ASDAS-CRP/ESR临床重要改善（CII，ΔASDAS≥1.1）等其它观察指标也得到了同样的结果：MRI+/CRP+组的达标率高于其他组。

结论：我们的研究发现，在2种及以上NSAIDs治疗失败的早期活动性nr-axSpA患者中，基线MRI骶髂关节炎以及升高的CRP对于骶髂关节炎症评分及更高的依那西普治疗反应率有正向预测价值。这个发现也有待于更大规模的研究来证实。

表

终点		MRI-/CRP-	MRI+/CRP-	MRI-/CRP+	MRI+/CRP+
ASAS40	ETN	2/17 (11.8)	8/32 (25.0)	3/11 (27.3)	20/35 (57.1)†
	PBO	2/21 (9.5)	6/42 (14.3)	1/10 (10.0)	7/31 (22.6)
ASAS20	ETN	7/17 (41.2)	14/32 (43.8)	7/11 (63.6)	24/35 (68.6)*
	PBO	5/21 (23.8)	16/42 (38.1)	3/10 (30.0)	13/31 (41.9)
ASDAS-CRP	ETN	5/17 (29.4)	12/31 (38.7)	6/11 (54.5)	27/35 (77.1)‡
	PBO	2/21 (9.5)	7/42 (16.7)	5/10 (50.0)	10/32 (31.3)
ASDAS-ESR	ETN	6/17 (35.3)	12/28 (42.9)	4/11 (36.4)	25/33 (75.8)‡
	PBO	3/21 (14.3)	9/42 (21.4)	2/10 (20.0)	8/29 (27.6)
BASDAI50	ETN	4/17 (23.5)	10/32 (31.3)	4/11 (36.4)	25/35 (71.4) ‡
	PBO	4/21 (19.0)	11/42 (26.2)	2/10 (20.0)	9/32 (28.1)
*p<0.05, †p<0.01, ‡p<0.001 vs PBO(安慰剂)。表中数值是达到观察终点的患者例数 n/N(%)。ASDAS-CRP/ESR相关数值是"临床重要改善"即ΔASDAS≥1.1