Baseline MRI and CRP As Predictors of Response to Etanercept in the Management of Patients with Non-Radiographic Axial Spondyloarthritis (nr-axSpA)

Matthew A. Brown¹, Paul A. Bird², Philip C. Robinson³, Philip J. Mease⁴, Filip van Den Bosch⁵, Christine Surian⁶, Zirke Wiid⁶, Heather Jones⁷, Annette Szumski⁸ and Lisa Marshall⁷, ¹Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, Australia, ²University of New South Wales, Sydney, Australia, ³University of Queensland & Royal Brisbane and Women's Hospital, Brisbane, Australia, ⁴Rheumatology Research, Swedish Medical Center, Seattle, WA, ⁵Department of Rheumatology, Ghent University Hospital, Ghent, Belgium, ⁶Pfizer Australia, Sydney, Australia, ⁷Inflammation Global Medical Affairs, Pfizer, Collegeville, PA, ⁸Department of Biostatistics, Pfizer, Collegeville, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: axial spondyloarthritis, C-reactive protein (CRP), etanercept and non-radiographic, MRI

Session Information

Date: Sunday, November 8, 2015

Title: Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment Poster I: Clinical Aspects and Assessments

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Treatment with tumor necrosis factor α (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 suggests 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). The objective of this study was to determine if MRI sacroiliitis positivity and/or elevated CRP at baseline are predictive of 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 AS, having BASDAI ≥4, and failure of ≥2 NSAIDs were randomized to 12 weeks of double-blind treatment with ETN 50 mg 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 hsCRP (elevated/normal [+/-]) status at baseline. MRI sacroiliitis positivity was defined according to the ASAS definition of a positive MRI result; elevated hsCRP was based on the ULN and defined as >3 mg/L.

Results: A total of 215 subjects (ETN, n=106; PBO, n=109) were included in these analyses. At baseline, breakdown according to MRI sacroiliitis and CRP status was: MRI-/CRP-, n=26; MRI+/CRP-, n=97; MRI-/CRP+, n=15; MRI+/CRP+, n=77. 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 those patients with MRI+/CRP+ at baseline and the lowest response was seen in the MRI-/CRP- subgroup. Similar observations were made for other clinical endpoints with a markedly higher proportion of MRI+/CRP+ patients achieving BASDAI 50 and clinically important improvement (Δ≥1.1) in ASDAS-CRP/ESR than those in the other MRI/CRP subgroups.

Endpoint		MRI-/CRP-	MRI+/CRP-	MRI-/CRP+	MRI+/CRP+
ASAS40	ETN	2/11 (18.2)	10/46 (21.7)	4/7 (57.1)	19/41 (46.3)^*
ASAS40	PBO	0/14 (0)	8/50 (16.0)	0/7 (0)	8/36 (22.2)
ASAS20	ETN	6/11 (54.5)	17/46 (37.0)	5/7 (71.4)	27/41 (65.9)
ASAS20	PBO	2/14 (14.3)	20/50 (40.0)	1/7 (14.3)	16/36 (44.4)
ASDAS-CRP	ETN	2/11 (18.2)	17/45 (37.8)^*	3/7 (42.9)	32/41 (78.0)^†
ASDAS-CRP	PBO	0/14 (0)	9/50 (18.0)	3/8 (37.5)	14/36 (38.9)
ASDAS-ESR	ETN	4/11 (36.4)	16/42 (38.1)	3/6 (50.0)	28/40 (70.0)^‡
ASDAS-ESR	PBO	1/14 (7.1)	11/50 (22.0)	1/6 (16.7)	10/35 (28.6)
BASDAI50	ETN	2/11 (18.2)	14/46 (30.4)	4/7 (57.1)^*	26/41 (63.4)^†
BASDAI50	PBO	2/14 (14.3)	13/50 (26.0)	0/8 (0)	11/36 (30.6)
*p<0.05, ^†p<0.01, ^‡p<0.001 vs PBO Values are patients achieving endpoint n/N (%). Values for ASDAS-CRP/ESR are patients achieving clinically important improvement Δ≥1.1

Conclusion: Our analyses suggest that in patients with early, active nr-axSpA and an inadequate response to ≥2 NSAIDs, a combination of MRI positivity and elevated hsCRP at baseline had a positive predictive value on joint inflammation score and clinical response of ETN subjects. A larger sample size is required to definitively test these findings. Further exploratory analyses are being undertaken to determine the predictive value of HLA-B27 status, gender and age on treatment response in each group.

Disclosure: M. A. Brown, Abbvie, Pfizer, UCB, Wyeth, Leo Pharma, NIAMS, NHMRC, Arthritis Australia, Qld Government, 2,Pfizer, Abbvie, UCB, 5,Pfizer, Abbvie, UCB, 8; P. A. Bird, Pfizer, Abbvie, Roche, Janssen, BMS, 8; P. C. Robinson, NHMRC, ARA, RACP, 2,Pfizer, UCB, Abbvie, Janssen, Menarini, 5,Menarini, Janssen, Abbvie, UCB, 8; P. J. Mease, AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, 2,AbbVie, Amgen, Biogen Idec, BMS, Celgene, Covagen, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, UCB, 5,AbbVie, Amgen, Biogen Idec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Pfizer, UCB, 8; F. van Den Bosch, Abbvie, Celgene, Novartis, Pfizer, UCB, 5,Abbvie, Celgene, Janssen, Novartis, Pfizer, UCB, 8; C. Surian, Pfizer Australia, 3; Z. Wiid, Pfizer Australia, 3; H. Jones, Pfizer, Inc, 3,Pfizer, Inc, 1; A. Szumski, InVentiv Health, 3; L. Marshall, Pfizer Inc, 1,Pfizer Inc, 3.

To cite this abstract in AMA style:

Brown MA, Bird PA, Robinson PC, Mease PJ, van Den Bosch F, Surian C, Wiid Z, Jones H, Szumski A, Marshall L. Baseline MRI and CRP As Predictors of Response to Etanercept in the Management of Patients with Non-Radiographic Axial Spondyloarthritis (nr-axSpA) [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/baseline-mri-and-crp-as-predictors-of-response-to-etanercept-in-the-management-of-patients-with-non-radiographic-axial-spondyloarthritis-nr-axspa/. Accessed .

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