Ab1093 long-term improvement in individual acr response criteria and residual disease in psoriatic arthritis patients treated with guselkumab: post hoc analysis of a phase 3 randomized, double-blind, placebo-controlled study

Background Treatment effects on PsA joint symptoms are assessed by ACR response rates, reflecting percentages of patients (pts) meeting a composite measure of improvement from baseline (BL) at specific timepoints. Alternatively, the ACR-numeric (ACR-N) is a continuous measure of improvement based on 7 ACR components. Objectives Contrast performance of ACR response rates with ACR-N in characterizing guselkumab (GUS) treatment effect in PsA and describe duration and extent of continuous improvement with GUS using ACR-N and ACR components through week (W) 100. Methods The phase 3 DISCOVER-2 trial enrolled bio-naïve adults with active PsA (swollen and tender joint counts [SJC/TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL). 739 pts were randomized (1:1:1) and treated with GUS 100 mg every 4W (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO) with crossover to GUS Q4W at W24. ACR20/50/70 response rates through W100 were determined using non-responder imputation (NRI) for missing data; GUS Q4W/Q8W and PBO rates were compared through W24. Duration of continuous improvement over 100W of GUS was assessed by contrasting least square mean (LSM) ACR-N and ACR component values between consecutive visits. Percent changes in SJC, TJC, physician global (MDGA), pt global (PtGA), health assessment quality disease index (HAQ-DI), CRP, and pt-pain were also assessed, adjusting for treatment group, BL use of csDMARDs, and respective BL scores. Results ACR response rates were significantly greater with GUS Q4W/Q8W vs PBO by W4 (ACR20), W8 (ACR50), and W8-12 (ACR70); significant differences in ACR-N between GUS Q4W/Q8W vs PBO were observed by W2 (GUS Q4W) or W8 (GUS Q8W) (Table 1; nominal p<0.05). Similar responses were observed with GUS Q4W and Q8W. Among GUS-treated pts, nominally significant improvements comparing ACR-N scores across consecutive visits were observed by W2, with a positive trajectory through W100 (Figure 1). Individual ACR components also significantly improved by W2 and – apart from CRP levels that rapidly plateaued to means <1 mg/dL – continued to improve vs previous visit through W68-84 of GUS (nominal p<0.05). Conclusion GUS rapidly improved PsA activity whether assessed by ACR response or ACR-N. Early response was apparent across ACR components, followed by a positive trajectory through 2 years of GUS that yielded low levels of residual disease. Table 1. ACR Response Rates (NRI) and ACR-N Scores Over Time With GUS (Q4W/Q8W) vs PBO ACR20 Achievement (% of Pts) ACR50 Achievement (% of Pts) ACR70 Achievement (% of Pts) ACR-N Score (LSM Estimate) W Q4W (N=245)/ Q8W (N=248) PBO →Q4W (N=246) Q4W (N=245)/ Q8W (N=248) PBO →Q4W (N=246) Q4W (N=245)/ Q8W (N=248) PBO →Q4W (N=246) Q4W (N=245)/ Q8W (N=248) PBO →Q4W (N=246) 2 10.6%/ 10.1% 8.1% 0.4%/ 1.6% 0.4% 0%/ 0% 0% 4.6/ 5.2 6.4 4 21.6%*/ 19.8%* 11.8% 3.3%/ 4.0% 1.2% 0.8%/ 0.4% 0.8% -1.3*/ 0.2 5.4 8 40.4%*/ 39.1%* 17.5% 11.4%*/ 10.1%* 4.1% 2.4%/ 3.6%* 0.8% -12.9*/ -10.6* 1.9 12 51.4%*/ 49.6%* 26.4% 17.1%*/ 19.0%* 6.1% 5.3%*/ 8.1%* 0.4% -21.5*/ -19.2* -3.3 16 56.7%*/ 55.2*% 34.6% 21.6%*/ 28.6%* 9.8% 8.6%*/ 13.7%* 0.8% -24.7*/ -25.1* -4.3 20 59.2%*/ 63.7%* 30.5% 30.2%*/ 31.9%* 16.7% 14.3%*/ 15.7%* 3.3% -30.7*/ -31.2* -4.7 24 64.9%*/ 64.9%* 34.6% 33.5%*/ 31.5%* 15.0% 13.5%*/ 18.5%* 4.5% -33.5*/ -34.1* -5.2 28 68.6%/ 67.7% 46.7% 38.8%/ 39.5% 22.0% 20.0%/ 20.2% 7.3% -39.4/ -39.9 -17.8 36 73.9%/ 74.6% 64.6% 42.9%/ 42.3% 37.4% 23.3%/ 26.2% 14.6% -44.2/ -44.6 -35.5 44 69.8%/ 74.6% 66.3% 44.5%/ 45.6% 41.9% 22.4%/ 28.2% 19.9% -43.9/ -46.2 -38.0 52 71.0%/ 74.6% 64.2% 45.7%/ 48.4% 41.1% 26.1%/ 27.8% 17.9% -45.0/ -46.4 -36.8 68 71.8%/ 78.6% 69.5% 52.7%/ 55.6% 44.7% 32.2%/ 32.7% 25.2% -49.8/ -52.6 -43.3 76 75.1%/ 75.4% 67.9% 53.1%/ 50.8% 45.9% 29.8%/ 33.1% 25.2% -50.4/ -52.2 -44.7 84 71.4%/ 75.8% 70.3% 51.4%/ 56.9% 49.2% 35.1%/ 38.3% 26.0% -50.9/ -56.3 -48.9 100 75.9%/ 73.8% 68.3% 55.9%/ 54.8% 47.6% 34.7%/ 35.5% 29.7% -53.0/ -52.4 -49.5 *p-value <0.05 vs PBO (assessed only for PBO-controlled period [grey shaded]). REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Peter Nash Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Samsung, Sun Pharma, and UCB, Grant/research support from: AbbVie, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Samsung, Sun Pharma, and UCB, Iain McInnes Shareholder of: Causeway Therapeutics and Evelo Compugen, Consultant of: AbbVie, Amgen, Astra Zeneca, Bristol Myers Squibb, Cabaletta, Compugen, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Astra Zeneca, Amgen, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, May Shawi Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Francois Nantel Shareholder of: Johnson & Johnson, Consultant of: Janssen, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB.