POS0926 NORMALIZATION OF HIGH SENSITIVITY CRP VERSUS CLINICAL RESPONSE TO IXEKIZUMAB AT WEEK 16 IN PATIENTS WITH RADIOGRAPHIC & NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: RESULTS FROM THE COAST STUDIES
Authors: Marzo-Ortega H. , Juanola X. , Okano T. , Schymura Y. , Bradley A. , Gerwien J. , Monsberger B. , Liu Leage S. , Aletaha D. , Østergaard M. 
Published: May 2021

Background:

C-reactive protein (CRP), an objective marker of inflammation, can be used to monitor treatment response to biologics in patients with axial spondyloarthritis (axSpA) in addition to evaluating signs & symptoms. CRP is not elevated in all patients with active axSpA questioning its validity as a universal biomarker of response. Ixekizumab (IXE) demonstrated efficacy in axSpA treatment irrespective of baseline (BL) CRP levels. However, response to IXE categorized on CRP change from BL is unknown.

Objectives:

To evaluate response to IXE treatment from BL through week (wk) 16 in patients with axSpA categorized according to change in high sensitivity (hs) CRP.

Methods:

COAST-V (NCT 02696785),-W (NCT02696798), & -X (NCT02757352), were phase 3, multicentre, randomized, controlled trials, investigating the efficacy of IXE 80 mg every 4 & 2 wks in patients with: r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs; COAST-V); or who were inadequate responders/intolerant to tumour necrosis factor inhibitors (TNFi; COAST-W); or who fulfilled Assessment of SpondyloArthritis International Society (ASAS) criteria for non-radiographic (nr)axSpA (COAST-X).

This post hoc analysis focuses on approved dosing regimens. Depending on BL and wk 16 hsCRP values, patients were categorised as stable low (hsCRP ≤5 mg/L at BL & ≤5 mg/L at wk 16), normalized (hsCRP >5 mg/L at BL & ≤5 mg/L at wk 16) or elevated (hsCRP >5 mg/L at wk 16, irrespective of BL hsCRP). An absolute cutoff of 5 mg/L was used as the stratification factor in all COAST studies. Data were analyzed by treatment arm. Each trial was analyzed separately.

For hsCRP subgroups, patient demographics & other characteristics at BL, as well as trajectory over time for the endpoints ASAS40 & Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 are described. Non-responder imputation was used for missing values.

Results:

In all studies at BL, disease activity & MRI SPARCC score were higher in normalized & elevated subgroups compared to the stable low subgroup - a.

In COAST-V, ASAS40 & BASDAI50 response was observed in IXE-treated patients regardless of hsCRP change status by wk 16 vs placebo. The highest ASAS40 & BASDAI50 response rate was reported in patients with normalized hsCRP - b. Similar findings were observed in COAST-W & -X.

Table 1.

Baseline Patient demographics & other characteristics - ITT population, per CRP subgroup

COAST-V
(r-axSpA, bDMARD naive)COAST-W
(r-axSpA, inadequate responders /intolerant to TNFi)COAST-X
(non-radiographic axSpA, bDMARD naïve)Stable low (n=79)Norma-lized (n=80)Elevated (n=98)Stable low
(n=58)Norma-lized (n=34)Elevated (n=126)Stable low (n=78)Norma-lized
(n=40)Elevated (n=81)ParameterAge (years)43.7 (12.1)38.9 (10.9)42.7 (12.0)50.4 (13.3)46.1 (13.8)45.7 (12.5)44.0 (12.8)37.2 (14.6)38.7 (12.8)Male gender, n (%)63 (79.7)71.0 (88.8)78 (79.6)39.0 (67.2)30 (88.2)109 (86.5)35 (44.9)23 (57.5)34 (42)Duration of symptoms since axSpA onset (years)17.5 (11.2)14.4 (9.3)16.1 (9.9)21.7 (12.9)16.8 (11.6)18.9 (10.9)12.1 (9.9)10.3 (9.7)9.5 (9.0)HLA-B27 positive, n (%)69 (87.3)75.0 (93.8)89 (90.8)31.0 (91.2)101 (80.2)101 (80.2)48 (61.5)31 (77.5)67 (82.7)BASDAI Total Score6.5 (1.4)6.7 (1.5)7.0 (1.1)7.4 (1.5)7.3 (1.3)7.4 (1.3)6.9 (1.5)7.1 (1.6)7.2 (1.5)ASDAS Total Score3.1 (0.5)3.9 (0.6)4.2 (0.7)3.5 (0.6)4.3 (0.6)4.4 (0.8)3.2 (0.6)4.2 (0.8)4.2 (0.9)Spinal Pain due to AS7.0 (1.5)7.0 (1.5)7.5 (1.3)7.8 (1.5)7.7 (1.5)7.9 (1.4)7.2 (1.7)7.5 (1.7)7.5 (1.6)Patients with peripheral articular manifestations (>=1 TJC or >=1 SJC)47 (59.5)40 (50)62 (63.3)43 (74.1)24 (70.6)86 (68.3)56 (71.8)33 (82.5)66 (81.5)MRI Spine SPARCC ScoreMRI SIJ SPARCC ScoreMRI SPARCC Score6.7 (11.2)21.8 (27.3)20.7 (25.7)1.2 (2.3)7.0 (7.6)10.4 (17.0)5.2 (6.6)6.1 (8.2)6.2 (10.5)

Conclusion:

IXE reduced clinical disease activity in patients with axSpA irrespective of hsCRP change from BL to wk 16. Improvement in hsCRP level was associated with overall response rates.

Acknowledgements:

The authors would like to acknowledge Philana Fernandes, an employee of Eli Lilly and Company, for her for writing and editorial support.

Disclosure of Interests:

Helena Marzo-Ortega Consultant of: Celgene, Janssen, Eli Lilly, Novartis, Pfizer, UCB, Grant/research support from: Janssen, Novartis, Xavier Juanola: None declared, Tadashi Okano Speakers bureau: Asahi Kasei, Astellas, Abbvie, Ayumi, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Novartis, Ono, Pfizer, Sanofi and Takeda, Grant/research support from: Asahi Kasei, Abbvie, Chugai, Eisai, Yves Schymura Employee of: Eli Lilly, Andrew Bradley Shareholder of: Eli Lilly, Employee of: Eli Lilly, Jens Gerwien Shareholder of: Eli Lilly, Employee of: Eli Lilly, Brigitte Monsberger Shareholder of: Eli Lilly, Employee of: Eli Lilly, Soyi Liu Leage Employee of: Eli Lilly, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi/Genzyme, Grant/research support from: Abbvie, Lilly, Novartis, Roche, Mikkel Østergaard Speakers bureau: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis, Pfizer, Roche, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene, Novartis