POS0943 GUSELKUMAB PROVIDES DURABLE IMPROVEMENTS IN PAIN AMONG PATIENTS WITH PSORIATIC ARTHRITIS AND AN INADEQUATE RESPONSE TO TNFi: COSMOS PHASE 3b TRIAL
Authors: L. C. Coates, G. Schett, M. A. D’agostino, J. Ramírez, M. Sharaf, E. Rampakakis, M. Koivunen, M. Zimmermann, F. Lavie, P. S. Helliwell
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients (pts) with psoriatic arthritis (PsA) report pain relief as a priority for treatment.<sup>[1]</sup> In prior analyses of a predominately bio-naïve population, guselkumab (GUS; an interleukin [IL]-23 inhibitor) treatment led to an early and significant improvement in pain at Week (W)2 vs placebo (PBO).<sup>[2]</sup> The pain response was sustained at 1 year.<sup>[2]</sup> <h3>Objectives:</h3> Using data from the COSMOS trial (NCT03796858), we sought to compare the effect of GUS vs PBO on pain assessed by several measures, and to evaluate the time course of pain improvement in pts with PsA and inadequate response to 1 or 2 tumour necrosis factor inhibitors (TNFi-IR). <h3>Methods:</h3> Adults with active PsA (swollen/tender joint counts [SJC/TJC], each ≥3) and TNFi-IR were randomized 2:1 to receive subcutaneous GUS 100 mg (n=189) or PBO (n=96) at W0, W4, then every 8 weeks thereafter. PBO pts crossed over to GUS at W16 (early escape [EE], n=45) or W24 (planned, n=51). In this <i>post hoc</i> analysis, through W24, pts with missing data or those who met treatment failure rules, including EE criteria, were imputed as non-responders. Through W24, least squares mean changes from baseline (BL) in pain measured via a visual analogue scale (VAS; 0–100 mm [lower score = less = pain]), the bodily pain domain of the 36-Item Short Form Health Survey (0–100 [higher score = less pain]), and investigator-assessed TJC (0–68 [lower score = less pain]) were estimated using a mixed-effects model for repeated measures, which included prior number of TNFi, BL use of conventional systemic disease-modifying antirheumatic drugs (csDMARDs), and BL pain score of the respective outcome as explanatory variables. The proportions of pts achieving minimal clinically important improvements in binary endpoints (≥15 mm on the pain VAS)<sup>[3]</sup> and clinically meaningful/substantial improvement (≥30/≥50% on the pain VAS)<sup>[3]</sup> through W24 are also described. Maintenance of pain response at W48 was assessed among pts who achieved response at W24, using as-observed data. Kaplan–Meier (KM) and Cox regression (adjusted for prior number of TNFi, and BL use of csDMARDs, and pain score) analyses were used to assess time to achievement of each binary endpoint through W24. All <i>P</i> values are nominal. <h3>Results:</h3> Among GUS- and PBO-randomized pts, mean BL values for pain VAS, bodily pain, and TJC were 64.6/60.3, 34.9/35.9, and 21.0/18.2, respectively. Numerically greater reductions in scores were observed with GUS vs PBO by the first timepoint assessed (W4), reaching statistical significance at W8 for TJC, W12 for pain VAS, and W16 for bodily pain (Figure 1). In the KM analyses, separation of GUS and PBO groups for meaningful pain improvement (≥15 mm and ≥30% improvement in pain VAS) occurred by the first assessment timepoint (Figure 2). The median number of weeks to achieve a ≥15 mm, ≥20%, and ≥30% improvement in pain VAS with GUS was 8, 8, and 12, respectively. A Cox regression analysis, adjusted for potential confounders, yielded consistent results. Of the GUS-randomized pts, response rates at W24 and W48 for a ≥15 mm, ≥30%, and ≥50% improvement in pain VAS were 47.6/61.4%, 42.3/58.7%, and 23.8/49.2%, respectively. Among pts who achieved ≥15 mm (n=104), ≥30% (n=92), and ≥50 (n=50) improvement in pain VAS at W24, 91.3%, 91.3%, and 88.0% of pts, respectively, maintained response at W48. <h3>Conclusion:</h3> In TNFi-IR PsA pts with a high burden of disease activity and substantial pain, early separation in pain response was observed between GUS- and PBO-treated groups, with a significantly higher proportion of GUS-randomized pts achieving meaningful improvements in pain. These findings are consistent with those observed in a large population of predominately bio-naïve pts.<sup>[2]</sup> Among pts who achieved pain endpoints at W24, ≥88% maintained response at W48, suggesting durable improvements in pain, even in a TNFi-IR PsA pt population. <h3>REFERENCES:</h3> [1] Gudu T <i>et al. Expert Rev Clin Immunol</i> 2018;14:405–17 [2] Nash P <i>et al</i>. Presented at EULAR congress, 1–4 June 2022, Copenhagen, Denmark. Poster 1070 [3] Dworkin RH <i>et al</i>. <i>J Pain</i> 2008;9:105–21 [4] Leung YY <i>et al. J Rheumatol</i> 2011;38:2077–9 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Laura C. Coates has received speakers fees and/or consulting fees and/or research grants from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen-Cilag GmbH, Medac, Moonlake, Novartis, Pfizer, and UCB Pharma, has received speakers fees and/or consulting fees and/or research grants from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen-Cilag GmbH, Medac, Moonlake, Novartis, Pfizer, and UCB Pharma, has received speakers fees and/or consulting fees and/or research grants from: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen-Cilag GmbH, Medac, Moonlake, Novartis, Pfizer, and UCB Pharma, Georg Schett: None declared, Maria Antonietta D'Agostino: None declared, Julio Ramírez has received speaker fees and/or instructor fees and/or consultant fees and/or research grants from: AbbVie, Amgen, Eli Lilly, Janssen-Cilag GmbH, Novartis, Pfizer, and UCB Pharma, has received speaker fees and/or instructor fees and/or consultant fees and/or research grants from: AbbVie, Amgen, Eli Lilly, Janssen-Cilag GmbH, Novartis, Pfizer, and UCB Pharma, has received speaker fees and/or instructor fees and/or consultant fees and/or research grants from: AbbVie, Amgen, Eli Lilly, Janssen-Cilag GmbH, Novartis, Pfizer, and UCB Pharma, has received speaker fees and/or instructor fees and/or consultant fees and/or research grants from: AbbVie, Amgen, Eli Lilly, Janssen-Cilag GmbH, Novartis, Pfizer, and UCB Pharma, Mohamed Sharaf is an employee of Janssen Pharmaceutical Companies of Johnson &amp; Johnson and owns Johnson &amp; Johnson stock, Emmanouil Rampakakis is an employee of JSS Medical Research, providing consulting services to Janssen-Cilag GmbH, Minni Koivunen is an employee of Janssen Pharmaceutical Companies of Johnson &amp; Johnson and owns Johnson &amp; Johnson stock and/or stock options, Miriam Zimmermann is an employee of Janssen Pharmaceutical Companies of Johnson &amp; Johnson and owns Johnson &amp; Johnson stock and/or stock options, Frédéric Lavie is an employee of Janssen Pharmaceutical Companies of Johnson &amp; Johnson and owns Johnson &amp; Johnson stock and/or stock options, Philip S Helliwell has received speaker and/or consulting fees from: AbbVie, Amgen, Eli Lilly; Novartis and Janssen-Cilag GmbH, has received speaker and/or consulting fees from: AbbVie, Amgen, Eli Lilly; Novartis and Janssen-Cilag GmbH.