Pos1547 efficacy of ust in active psa monitored by musculoskeletal ultrasound is independent from concomitant mtx use: subgroup analysis from a randomized placebo-controlled investigator initiated clinical trial

Background BDMARD treatments in patients with psoriatic arthritis (PsA) are initiated after insufficient response to csDMARD either in monotherapy or by in parallel continuing csDMARDs. Here, the value of MTX in combination with bDMARDs in PsA is still unclear. We designed an investigator-initiated, randomized, placebo-controlled trial (IIT) in active PsA to examine the potential impact of MTX-continuation or -initiation parallel to newly started UST on different outcomes beyond clinical examination (MSUS; PsASon22 score [1]). Objectives To compare sensitive imaging efficacy outcomes measured by MSUS changes [PsASon22] from week 4 and 24 to baseline in UST+PBO vs UST+MTX (stratified to ongoing or new onset of MTX treatment). Methods A total of 186 patients with active PsA (defined as TJC≥4, SJC≥4 [68/66 joint count] and DAS28≥3.2) were screened for eligibility. 173 patients were randomized to UST+MTX (new or ongoing) or UST+PBO. 84 patients were included in the subgroup analysis with MSUS scoring of PsASon22 at BL, weeks 4 and 24. Results were compared between the groups with prior MTX treatment (UST+ ongoing MTX or UST+PBO) and with new initiation of MTX to UST (UST+ new MTX or UST+PBO) according to the study design. Results BL data were well-balanced between treatment groups (UST+MTX, n=44; UST+PBO, n=40) and subgroups with exception of slightly higher age (mean age 53.3 years) and more (45%) female patients in the UST with ongoing MTX group. All baseline data are shown in Table 1. After UST initiation, improvement of inflammatory activity measured by MSUS using PsASon22 score was seen early at week 4 in all treatment groups. The improvement was delayed in patients with previous MTX failure (“prior MTX”) and, in overall less pronounced compared to the patients without previous MTX treatment (Figure 1). At week 24, clinical meaningful changes in PsASon22 score were seen in all treatment groups but with most prominent differences in both treatment groups with UST+PBO. Conclusion IL12/23 inhibition with UST is an effective treatment for active PsA independent of MTX use. Data from this IIT indicate that additional MTX has no positive impact on UST efficacy for musculoskeletal manifestations such as arthritis and enthesitis measured sensitively by PsASon22 ultrasound score validated for PsA monitoring. Moreover, by monitoring in MSUS, patients on UST monotherapy seem to benefit best from the treatment. Reference [1]Ficjan, A., et al., Ultrasound composite scores for the assessment of inflammatory and structural pathologies in Psoriatic Arthritis (PsASon-Score). Arthritis Res Ther, 2014. 16(5): p. 476. Table 1. Baseline Characteristics: Subgroup analysis on MSUS Parameters with prior MTX, UST + MTX with prior MTX, UST + Placebo without MTX, UST + MTX without MTX, UST + Placebo N=20 N=17 N=24 N=23 Age [years] 53.3 (SD 10.0) 46.8 (SD 15.8) 45.5 (SD 14.6) 45.2 (SD 15.6) Sex [Female] 9 (45.0%) 6 (35.3%) 9 (37.5%) 8 (34.8%) BMI [kg/m²] 28.0 (SD 6.1) 28.5 (SD 5.5) 30.4 (SD 4.7) 28.1 (SD 4.8) Age at PsA diagnosis [years] 47.8 (SD 12.2) 42.5 (SD 15.0) 42.0 (SD 14.0) 40.6 (SD 16.2) PsASon22 5.0 (1.5 to 13.0) 2.0 (1.0 to 8.0) 3.0 (1.0 to 7.0) 6.0 (3.0 to 10.0) Presence of Enthesitis [LEI > 0] 9 (45.0%) 7 (41.2%) 16 (66.7%) 11 (47.8%) Presence of Dactylitis [LOCF] 1 (5.0%) 1 (5.9%) 13 (54.2%) 9 (39.1%) TJC68 [LOCF] 14.5 (9.0 to 23.5) 13.0 (9.0 to 16.0) 10.5 (8.0 to 15.0) 13.0 (9.0 to 18.0) SJC66 [LOCF] 8.5 (6.5 to 20.5) 8.0 (6.0 to 10.0) 8.0 (7.0 to 12.0) 8.0 (5.0 to 10.0) Nail involvement [mtNAPSI > 0] 7 (35.0%) 9 (52.9%) 17 (70.8%) 14 (60.9%) BSA [%] 2.0 (1.0 to 6.0) 1.0 (1.0 to 3.0) 5.5 (1.0 to 12.1) 2.0 (1.0 to 5.0) PASI 2.5 (0.7 to 5.8) 1.8 (0.6 to 3.8) 7.1 (2.5 to 10.4) 4.2 (0.8 to 8.2) HAQ-DI [LOCF] 0.8 (0.4 to 1.4) 0.9 (0.3 to 1.5) 1.1 (0.4 to 1.6) 1.0 (0.4 to 1.3) DLQI [LOCF] 5.5 (3.0 to 12.5) 6.0 (1.0 to 9.0) 11.5 (3.0 to 15.5) 6.0 (3.0 to 11.0) EQ5D Health Scale VAS100 [LOCF] 47.7 (SD 24.1) 50.2 (SD 20.2) 54.2 (SD 22.9) 59.1 (SD 16.0) Figure 1. Improvement in PsASon22 score from baseline to week 4 and 24 (mITT population) Acknowledgements: NIL. Disclosure of Interests Michaela Köhm Speakers bureau: Janssen, UCB, Pfizer, Novartis, Consultant of: Janssen, UCB, Pfizer, Novartis, Grant/research support from: Janssen, Pfizer, GSK, BMS, Ann Christina Foldenauer Grant/research support from: Janssen, GSK, BMS, Pfizer, Tanja Rossmanith Grant/research support from: Janssen, GSK, Leo, Pfizer, BMS, Siegfried Wassenberg: None declared, Stephanie Finzel: None declared, Arnd Kleyer: None declared, Raoul Bergner: None declared, Rieke Alten: None declared, Herbert Kellner: None declared, Jochen Walter: None declared, Peter Kästner: None declared, Frank Behrens Speakers bureau: Janssen, Pfizer, UCB, Novartis, Consultant of: Janssen, Pfizer, UCB, Novartis, Grant/research support from: Janssen, Pfizer, UCB, Novartis, GSK, BMS.