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 ).

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