POS0901 IXEKIZUMAB SHOWS A DISTINCT PATTERN OF PAIN IMPROVEMENT BEYOND INFLAMMATION IN RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS
Authors: De Vlam K. , Gallo G. , Mease P. J. , Rahman P. , Krishnan V. , Sandoval D. , Lin C. Y. , Bolce R. , Conaghan P. G. 
Published: May 2021

Background:

The efficacy of ixekizumab (IXE) in biologic-naïve patients with radiographic axial spondyloarthritis (r-axSpA) has been previously presented using traditional axSpA outcome measures, such as BASDAI and ASAS.

Objectives:

In patients with active r-axSpA, to assess the analgesic efficacy of IXE as it relates to patient-reported and objective measures of inflammation.

Methods:

The Phase III COAST-V (NCT02696785) multi-center, randomized, double-blind, placebo (PBO)-controlled and active reference arm with adalimumab (ADA) trial investigated the efficacy of IXE in 341 patients (pts) with active r-axSpA for 52 weeks (W). Pts were initially randomized to IXEQ4W, IXEQ2W, PBO, and ADAQ2W. At W16, pts assigned to PBO and ADA were re-randomized to IXEQ2W or Q4W. Changes in spinal pain at night (SP-N) and spinal pain were measured at each study visit and analysed while controlling for CRP levels or mean of BASDAI questions 5 & 6 (Q5: Duration and Q6: Intensity of morning stiffness). Observed data analyses are presented for each group stratified by treatment arm and compared to PBO. In the initial analysis, pts were categorized into 2 sub-groups defined as “Sustained” and “Fluctuating” depending on: CRP <5 mg/L W4-16 vs. CRP ≥5 mg/L at any point beyond W4 between weeks 4-16 respectively. In a second analysis, pts were categorized based on BASDAI Q5/6 improvement: “Sustained” if ≥2-pt improvement W12-16 vs. “Fluctuating” if <2-pt improvement at any point beyond W12 between W12-16.

Results:

Between W0 and W16, pts treated (tx) with IXEQ4W experienced greater reduction in SP-N than pts tx with ADA, in both CRP sustained and fluctuating groups (Fig 1a). Pts in the IXEQ4W and ADA arms showed different trajectories of pain improvement in the CRP fluctuating groups. For the pts with a fluctuating CRP ≥5 mg/L, pts in IXEQ4W arm demonstrated a greater reduction in SP-N compared to pts in PBO arm (p < .001) at W16, whereas pts in ADA arm did not experience a reduction in SP-N compared to PBO (p = .416). For the pts with a sustained CRP <5mg/L, IXEQ4W and ADA treatments both significantly demonstrated reduction in SP-N compared to PBO at W16 (IXEQ4W: p = .002; ADA: p = .02), with IXEQ4W treatment showing a greater level of reduction (Fig 1a). The pts randomized to ADA and re-randomized to IXEQ2W or Q4W (ADA/IXE) experienced further improvement in SP-N. This effect was sustained over the 52-wk period (Fig 1b). The same pattern of improvement in SP-N was observed when controlling for the BASDAI Q5/6; the SP-N improvement was greater in pts with a sustained BASDAI Q5/6 compared to pts with a fluctuating BASDAI Q5/6, regardless of treatment (Table 1). In the fluctuating BASDAI Q5/6, for pts in ADA/IXE arm, further reduction of both spinal pain and SP-N were observed (Table 1).

Table 1.

Change in Pain Outcome at baseline, week 16 and week 52 by Inflammation Status as assessed by BASDAI or CRP levels for patients receiving placebo (PBO), adalimumab (ADA), and ixekizumab every 4 weeks (IXE Q4W)

Change from baselinePBOADAIXEQ4WbaselineWeek 16
(as observed)Week 52
PBO/IXE
(as observed)baselineWeek 16
(as observed)Week 52
ADA/IXE
(as observed)baselineWeek 16
(as observed)Week 52
(as observed)Spinal painBASDAI Q5/6 sustained7.54-3.33-4.657.21-4.07-4.57.4-4.52-4.94BASDAI Q5/6 fluctuating7.37-1.32-2.826.76-1.2-2.246.97-1.3-2.52CRP sustained7-1.53-1.936.83-2.9-3.67.23-3.57-4.21CRP fluctuating7.51-1.96-3.637.28-2-2.897.24-2.91-3.93Spinal pain at nightBASDAI Q5/6 sustained7.12-3.21-4.617.26-4.63-4.927.12-4.73-4.91BASDAI Q5/6 fluctuating7.05-1.15-2.886.6-1.2-2.497.03-2.17-2.92CRP sustained7.2-1.87-2.276.76-3.2-3.856.89-3.8-4.12CRP fluctuating7.04-1.69-3.67.24-2.21-3.397.35-3.68-4.38

Conclusion:

IXE reduced SP-N and spinal pain irrespective of CRP or morning stiffness. Additionally, pts treated with ADA re-randomized to IXE experienced a further reduction in SP-N and spinal pain. Collectively, these results support the additive benefits of IXE in reducing pain above measurable effects on inflammation.

Acknowledgements:

The authors would like to thank Eglantine Julle-Daniere for writing and editorial contributions

Disclosure of Interests:

Kurt de Vlam Speakers bureau: Eli Lilly, Novartis, Pfizer, Paid instructor for: Celgene, Amgen, Consultant of: Elil Lillyn Novartis, UCB, Galapagos, Sandoz, Pfizer, Grant/research support from: Celgene, Gaia Gallo Shareholder of: Eli Lilly, Employee of: Eli Lilly, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sun, UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, Sun, UCB, Proton Rahman Speakers bureau: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Grant/research support from: Janssen, Novartis, Venkatesh Krishnan Shareholder of: Eli Lilly, Employee of: Eli Lilly, David Sandoval Shareholder of: Eli Lilly, Employee of: Eli Lilly, Chen-Yen Lin Shareholder of: Eli Lilly, Employee of: Eli Lilly, Rebecca Bolce Shareholder of: Eli Lilly, Employee of: Eli Lilly, Philip G Conaghan Consultant of: personal fees from: AbbVie, AstraZeneca, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer