Modification of Structural Lesions on Magnetic Resonance Imaging By Etanercept: A 12-Week Randomized Placebo-Controlled Trial

Walter Maksymowych¹, Stephanie Wichuk², Maxime Dougados³, Heather Jones⁴, Annette Szumski⁵, Lisa Marshall⁴, Jack F Bukowski⁶ and Robert G Lambert⁷, ¹Department of Medicine, University of Alberta, Edmonton, AB, Canada, ²Rheumatology Research Lab, University of Alberta, Edmonton, AB, Canada, ³Rheumatology Department, Hôpital Cochin, Paris, France, ⁴Inflammation Global Medical Affairs, Pfizer, Collegeville, PA, ⁵Department of Biostatistics, Pfizer, Collegeville, PA, ⁶Clinical Affairs, Pfizer, Collegeville, PA, ⁷Department of Radiology & Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: axial spondyloarthritis, etanercept and inflammation, Lesions, MRI

Session Information

Date: Monday, November 9, 2015

Title: Imaging of Rheumatic Diseases II: MRI, PET and CT

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Modification
of structural lesions by anti-TNF therapy has not been demonstrated in a
randomized placebo (PBO)-controlled trial. The Spondyloarthritis
Research Consortium of Canada (SPARCC) sacroiliac joint (SIJ)
score
(SSS) assesses the degree of fat metaplasia (new tissue growth after resolution
of inflammation), erosion, backfill (new tissue growth at erosion site), and
ankylosis observed on MRI in the SIJ. This analysis evaluated the impact on
these lesions at 12 wks in patients with non-radiographic axial SpA receiving PBO
or etanercept (ETN) in the EMBARK study (ClinicalTrials.gov: NCT01258738).

Methods: Patients
had axial SpA per Assessment of SpondyloArthritis international Society (ASAS) criteria
without meeting modified NY radiographic criteria; BASDAI score ≥4; symptoms
for >3 months and <5 yrs; and had failed ≥2 NSAIDs. Patients were
randomized to double-blind ETN 50 mg/wk or PBO for 12 wks, then received
open-label ETN. Structural lesions were scored using the SPARCC SSS method on
T1-weighted spin echo (T1WSE) MRI. Two readers independently scored baseline
(BL) and 12-wk T1WSE MRI scans, blinded to patients, time point, and inflammation
scores assessed by short tau inversion recovery MRI scans. Readers’ mean
scores were used.

Results: Mean
(SD) age was 32 (7.8) yrs, 60.5% were male, duration of disease symptoms was 2.4
(1.8) yrs, 71.6% were human leukocyte antigen B27+, and 80.9% had sacroiliitis
on MRI (modified intent-to-treat [mITT] population, N=215). MRI
scans from 185 patients (ETN, n=88; PBO, n=97) with BL and 12-wk scans were
reviewed. At BL, there were no significant differences in mean SPARCC SSS
scores between ETN and PBO (table). From BL to 12 wks, change
in mean SPARCC SSS score was significantly greater for ETN than PBO for erosion
(-0.57
vs -0.08, respectively, p=0.009) and backfill (0.36
vs 0.06, p=0.021). This treatment difference is also presented in cumulative
probability plots (figure).

Conclusion: Treatment
with ETN was associated with significantly greater reduction in erosion and
increase in backfill at 12 wks vs. PBO, consistent with a very early reparative
response to anti-TNF therapy. The impact of this new data on disease
progression in SpA should be studied further.

Table. SPARCC SSS scores at baseline, week 12, and change from baseline to week 12
		ETN N=88	PBO N=97	P-value* ETN vs PBO Δ BL to week 12
Erosion	Baseline	2.25 (0.33)	1.73 (0.32)	0.009
	Week 12	1.68 (0.25)	1.65 (0.30)
	Δ BL to week 12	-0.57 (0.16)	-0.08 (0.10)
Backfill	Baseline	0.76 (0.22)	0.64 (0.20)	0.021
	Week 12	1.13 (0.29)	0.70 (0.23)
	Δ BL to week 12	0.36 (0.12)	0.06 (0.06)
Fat Metaplasia	Baseline	0.50 (0.19)	0.27 (0.09)	ns
	Week 12	0.56 (0.22)	0.32 (0.10)
	Δ BL to week 12	0.06 (0.07)	0.05 (0.05)
Ankylosis	Baseline	0.15 (0.10)	0.13 (0.11)	ns
	Week 12	0.15 (0.11)	0.13 (0.11)
	Δ BL to week 12	0.01 (0.01)	0.01 (0.01)
Values are mean (standard error). Observed case analysis, mITT population. *2-sample t-test. BL SPARCC SSS scores did not differ significantly between ETN and PBO. Treatment differences in Δ BL to week 12 for erosion and backfill remained significant after adjusting for BL SPARCC SSS scores using analysis of covariance models. Δ, change; ns, non-significant.

Figure.
Cumulative probability of change from baseline to week 12 in the etanercept and
placebo groups for (A) erosion and (B) backfill.

Disclosure: W. Maksymowych, Abbvie, 5,Amgen, 5,Eli Lilly and Company, 5,Janssen Pharmaceutica Product, L.P., 5,Pfizer Inc, 5,UCB, 5,Abbvie, 2,Boehringer Ingelheim, 5; S. Wichuk, None; M. Dougados, Pfizer Inc, 5,UCB, 5,AbbVie, 5,Merck Pharmaceuticals, 5; H. Jones, Pfizer, Inc, 3,Pfizer, Inc, 1; A. Szumski, InVentiv Health, 3; L. Marshall, Pfizer Inc, 1,Pfizer Inc, 3; J. F. Bukowski, Pfizer Inc, 3; R. G. Lambert, None.

To cite this abstract in AMA style:

Maksymowych W, Wichuk S, Dougados M, Jones H, Szumski A, Marshall L, Bukowski JF, Lambert RG. Modification of Structural Lesions on Magnetic Resonance Imaging By Etanercept: A 12-Week Randomized Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/modification-of-structural-lesions-on-magnetic-resonance-imaging-by-etanercept-a-12-week-randomized-placebo-controlled-trial/. Accessed .

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