ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1865

Ixekizumab Significantly Improves Self-Reported Overall Functioning and Health in Patients with Active As/Radiographic Axial Spa Naive to Biologic DMARD Therapy: 16‑Week Results of a Phase 3 Randomized, Active and Placebo-Controlled Trial

Uta Kiltz1, Désirée van der Heijde2, Annelies Boonen3,4, Lianne S. Gensler5, Theresa Hunter6, Fangyi Zhao6, Hilde Carlier6 and Jürgen Braun1,7, 1Rheumazentrum Ruhrgebiet, Herne, Germany, 2Leiden University Medical Centre, Leiden, Netherlands, 3Department of Medicine, Division of Rheumatology, Maastricht University Medical Center, Maastricht, Netherlands, 4Caphri Research Institute, Maastricht, Netherlands, 5School of Medicine, UCSF, San Francisco, CA, 6Eli Lilly and Company, Indianapolis, IN, 7Ruhr Universität Bochum, Bochum, Germany

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords:

Session Information

Date: Monday, October 22, 2018

Title: 4M089 ACR Abstract: Spondyloarthritis Incl PsA–Clinical III: Treatment of Axial SpA (1864–1869)

Session Type: ACR Concurrent Abstract Session

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

Background/Purpose: The Assessment of SpA international Society Health Index (ASAS HI) is a relatively new measure to assess function, disability, and health in patients with SpA. These are the first data of the ASAS HI in a Phase 3 study testing sensitivity to change and discrimination between active treatment and placebo (PBO).

Methods: The ASAS HI was assessed in biologic DMARD (bDMARD)-naive patients with active radiographic axial SpA (r-axSpA) in a Phase 3 study of ixekizumab (IXE), an IL-17A monoclonal antibody (COAST-V [NCT02696785]). The ASAS HI consists of 17 dichotomous items, total score ranging from 0 (good health) to 17 (poor health). Scores ≤5 are considered “Good health state,” while the smallest detectable change (SDC) is 3. In COAST-V, the scale was administered at screening, baseline, and Weeks 4, 8, and 16 to adults with active r-axSpA per ASAS criteria (sacroiliitis defined centrally by modified New York Criteria and ≥1 SpA feature), BASDAI ≥4, back pain ≥4, and inadequate response or intolerance to NSAID therapy. Patients were randomized 1:1:1:1 to PBO, adalimumab (ADA) 40 mg every 2 weeks (Q2W), or IXE 80 mg every 4 weeks (Q4W) or Q2W up to Week 16. Change from baseline in ASAS HI was analyzed using a mixed-effects model of repeated measures (MMRM). Categorical analyses were performed using a logistic regression model. Association between ASAS HI changes with clinical response was assessed using ANCOVA.

Results: Changes from baseline in ASAS HI total score at Weeks 4, 8, and 16 are presented in Figure. The ASAS HI separated between PBO and all active treatment groups at all time points. At Week 16, ASAS HI scores in the IXE Q4W, IXE Q2W, and ADA groups had improved by ≥3 (SDC) in 41.8%, 50.6%, and 42.7%, respectively, versus 34.5% in the PBO group. At Week 16, the percentage of patients in ASAS HI Good health state in the IXE Q4W, IXE Q2W, and ADA groups were 46.3%, 45.6%, and 40.3%, respectively, versus 25.0% in the PBO group. In patients treated with IXE, better ASAS20/ASAS40 responses were associated with greater improvements in ASAS HI scores at Week 16 (Table).

Conclusion: The ASAS HI separated at all time points between actively-treated and PBO‑treated patients. This proves good discrimination of this new outcome measure. In a Phase 3 study of bDMARD-naive patients with r-axSpA, those treated with ixekizumab experienced significantly better ASAS HI outcomes than PBO, with the best outcomes occurring in ASAS40 responders.

Study Sponsor Statement: This study was supported by Eli Lilly and Company. Lilly participated in the study design, data collection, and the analysis and reporting of study results.

 

Table. Association between ASAS HI Change from Baseline and Clinical Outcomes at Week 16

 

ASAS20 Nonresponder

Patient Achieving ASAS20 But Not ASAS40

ASAS40 Responder

All IXE (Mean [SD] Baseline ASAS HI Score = 7.9 [3.5])

N

55

27

82

ASAS HI (LSM [SE])

-0.7 (0.3)

-1.6 (0.5)

-4.1 (0.3)***,§

IXE Q4W (Mean [SD] Baseline ASAS HI Score = 7.5 [3.3])

N

29

13

39

ASAS HI (LSM [SE])

-0.4 (0.5)

-1.4 (0.7)

-3.9 (0.4)***,‡

IXE Q2W (Mean [SD] Baseline ASAS HI Score = 8.4 [3.6])

N

26

14

43

ASAS HI (LSM [SE])

-1.0 (0.5)

-1.8 (0.7)

-4.3 (0.4)***, ‡

Adalimumab (Mean [SD] Baseline ASAS HI Score = 8.2 [3.7])

N

37

21

32

ASAS HI (LSM [SE])

-0.7 (0.4)

-1.8 (0.5)

-4.6 (0.4)***,§

Placebo (Mean [SD] Baseline ASAS HI Score = 8.1 [3.5])

N

51

19

16

ASAS HI (LSM [SE])

-0.7 (0.3)

-1.5 (0.5)

-3.3 (0.6)***,†

ASAS HI = Assessment of SpA International Society Health Index; IXE = ixekizumab; Q2W = every 2 weeks; Q4W = every 4 weeks.

***p<.001 versus ASAS20 nonresponders.

†p<.05; ‡p<.01; §p<.001 versus ASAS20 responder/ASAS40 nonresponder group.

Note: An analysis of covariance model with change in ASAS HI score as dependent variable and ASAS status and baseline ASAS HI as independent variables was applied. Post hoc comparison was conducted with Scheffe’s correction.

 

Disclosure: U. Kiltz, AbbVie Inc., 2, 5,Chugai, 2, 5,Eli Lilly and Co., 2, 5,Grunenthal, 2, 5,Janssen, 2, 5,MSD, 2, 5,Novartis, 2, 5,Pfizer, Inc., 2, 5,Roche, 2, 5,UCB, Inc., 2, 5; D. van der Heijde, Imaging Rheumatology BV, 3,AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma, 5; A. Boonen, Eli Lilly and Co., 5; L. S. Gensler, AbbVie Inc., 2,Amgen Inc., 2,Novartis, 2, 5,UCB, Inc., 2,Galapagos, 5,Janssen, 5,Eli Lilly and Co., 5,Pfizer, Inc., 5; T. Hunter, Eli Lilly and Company, 1, 3; F. Zhao, Eli Lilly and Company, 1, 3; H. Carlier, Eli Lilly and Company, 1, 3; J. Braun, None.

To cite this abstract in AMA style:

Kiltz U, van der Heijde D, Boonen A, Gensler LS, Hunter T, Zhao F, Carlier H, Braun J. Ixekizumab Significantly Improves Self-Reported Overall Functioning and Health in Patients with Active As/Radiographic Axial Spa Naive to Biologic DMARD Therapy: 16‑Week Results of a Phase 3 Randomized, Active and Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/ixekizumab-significantly-improves-self-reported-overall-functioning-and-health-in-patients-with-active-as-radiographic-axial-spa-naive-to-biologic-dmard-therapy-16%e2%80%91week-results-of-a-phase-3-r/. Accessed .

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