AB0898 Guselkumab improves dactylitis in PsA patients with inadequate response to TNFi: data from the Phase 3b COSMOS trial

Abstract

BackgroundDactylitis is a biomarker of disease severity in psoriatic arthritis (PsA) associated with functional disability, impaired quality of life and radiographic progression. The COSMOS study demonstrated the efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit inhibitor (i), in patients (pts) with PsA who had inadequate response (IR; insufficient efficacy or intolerance) to 1–2 TNFi.1ObjectivesEvaluate the effect of GUS 100 mg Q8W on dactylitis, and assess the relationship between dactylitis resolution and improvement in other clinical outcomes, through 1 year in TNFi-IR PsA pts.MethodsPts received GUS or placebo (PBO); PBO pts crossed over to GUS at either Week (W) 16 (early escape [EE], n=45/96) or W24 (planned, n=51/96). Each of 20 digits was determined by the investigator to have no (0) to severe (3) dactylitis (Dactylitis Severity Scale [DSS]; total score: 0–60). Presence of dactylitis was defined by DSS score ≥1; complete or partial resolution was defined as a DSS score=0, or lower than baseline (BL), respectively. Change in DSS from BL at W24 was a secondary endpoint. Other clinical response outcomes including DAPSA LDA/remission, MDA and enthesitis resolution (Leeds Enthesitis Index score=0) were assessed by dactylitis resolution status. Both as observed and non-responder imputation (NRI; for missing data or EE) data are presented.ResultsOf 285 pts, 103 (36%; 67 GUS, 36 PBO) had dactylitis and 190 (67%) had enthesitis at BL. The majority of pts with dactylitis (76%) also had enthesitis. Pts with dactylitis had more severe joint and skin disease than those without (Table 1).Table 1.BL characteristics for TNFi-IR PsA pts with/without dactylitisWith dactylitisWithout dactylitisN103182Age, mean years (SD)48.3 (11.8)49.6 (12.5)Sex: male, %5048Years since PsA diagnosis; mean (SD)8.1 (7.2)8.6 (7.8)BMI, mean kg/m2 (SD)28.5 (5.8)30.1 (6.6)PsA characteristicsSwollen joint count, 0–66; mean (SD)12.3 (8.1)8.5 (4.8)Tender Joint count, 0–68; mean (SD)22.0 (12.9)19.1 (12.2)DAPSA score; mean (SD)48.6 (20.9)41.2 (16.8)Spondylitis with peripheral arthritis, %2824Enthesitis, %7662Psoriasis characteristics, mean (SD)  PASI score, 0–7214.5 (12.7)8.8 (9.6)  BSA, %23.4 (23.6)12.4 (17.1)  DLQI score, 0–3014.1 (7.0)12.6 (6.9)In an as-observed analysis of pts with BL dactylitis, numerically more GUS- (55%) than PBO- (33%) treated pts achieved complete dactylitis resolution at W16. By W48, 80% of GUS-randomized pts achieved complete resolution (NRI: 57% at W24, 67% at W48; Figure 1).Among 12 GUS pts with persistent dactylitis at W48, 9 (75%) had partial resolution. The 36 PBO pts with dactylitis crossed over to GUS at W16 (n=23; EE) or W24 (n=13; planned). As observed, 88% of these PBO→GUS pts had complete resolution of dactylitis at W48 (Figure 1).Of 105 dactylitis-free pts at BL in the GUS arm, 8 (8%) developed dactylitis before W48: 4 at W4, 2 at W8 and 1 each at W16 and 36. Complete resolution was seen in 6 (75%) of the 8 pts by W48, when 1 further new-onset case occurred.Utilizing observed data among GUS-randomized pts with and without BL dactylitis, 32% and 34%, respectively, achieved MDA at W48. Respective response rates were 59% and 55% for DAPSA LDA, and 28% and 15% for DAPSA remission. In those who did and did not achieve complete dactylitis resolution at W48, respective response rates were 38% and 0% for MDA, 68% and 13% for DAPSA LDA, and 31% and 0% for DAPSA remission. Of 69 pts with both enthesitis and dactylitis at BL who continued to receive GUS through W48, GUS resolved both manifestations in 72%, neither in 16%, only enthesitis in 4%, and only dactylitis in 7% of pts.ConclusionComplete dactylitis resolution was achieved in ≥80% of pts who continued to receive GUS at W48, with partial resolution seen in most remaining pts in an as-observed analysis. Response rates increased through W48. Dactylitis resolution in this difficult-to-treat TNFi-IR PsA population was frequently associated with enthesitis resolution and achievement of clinical outcomes representing low levels of disease activity.