Thresholds for efficacy outcomes in psoriatic arthritis vary according to baseline disease activity but not according to prior tumour necrosis factor inhibitor treatment.

IntroductionPatterns of treatment response can inform clinical decision-making. This study assessed the course and impact of achieving minimal clinically important improvement (MCII) in clinical measures and patient-reported outcomes (PROs) with guselkumab in patients with active psoriatic arthritis (PsA).MethodsPost hoc analyses evaluated 1120 patients with PsA receiving guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo from DISCOVER-1 (31% tumor necrosis factor inhibitor-experienced) and DISCOVER-2 (biologic-naïve). Achievement of MCII in clinical Disease Activity Index for PsA (cDAPSA), patient global assessment (PtGA) of arthritis, PtGA of psoriasis, patient-reported pain, Functional Assessment of Chronic Illness Therapy-Fatigue, Health Assessment Questionnaire-Disability Index, 36-item Short-Form Health Survey Physical Component Summary score, PtGA Arthritis + Psoriasis, and PsA Disease Activity Score (PASDAS) was compared between the guselkumab and placebo groups using Cox regression. Logistic regression adjusting for baseline factors evaluated associations between early (W4/W8) MCII achievement and stringent response (≥%50/%70 improvement in American College of Rheumatology response criteria, cDAPSA low disease activity [LDA], PASDAS LDA, and minimal disease activity) at W24/W52 among guselkumab-randomized patients.ResultsAmong patients with highly active PsA (baseline cDAPSA = 44.1–45.0, PASDAS = 6.4–6.5), times to MCII were significantly faster for guselkumab vs. placebo (hazard ratios 1.3–2.5; P < 0.05). Across measures, at first timepoint assessed, MCII rates were significantly higher with guselkumab (Q4W/Q8W 28–68%/29–65%) vs. placebo (19–47%; both P < 0.05). Early (W4/W8) MCII with guselkumab associated with higher odds of achieving stringent responses at W24/W52 (odds ratios 1.4–17.2/1.4–5.4).ConclusionsIn a mixed PsA population, significant proportions of patients treated with guselkumab achieved early (W4/W8) MCII across clinical and PRO measures, which associated with a higher likelihood of attaining clinically relevant improvements and low levels of disease activity at W24/W52.Trial registrationDISCOVER-1 (NCT03162796).DISCOVER-2 (NCT03158285).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-024-00702-0.

The Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA) are composite PsA disease activity measures. We sought to identify the PASDAS and DAPSA cut-off points consistent with patient acceptable symptom state (PASS), the threshold of symptoms beyond which patients consider themselves well, and examine PASS across published PASDAS and DAPSA thresholds for low, moderate and high disease activity. We used a standard protocol including physician assessment and patient-reported outcomes to prospectively record measures required to calculate PASDAS and DAPSA. We identified PASS thresholds for the PASDAS and DAPSA using receiver operating characteristics curve analyses. We assessed the frequency of reporting acceptable symptom state across disease activity thresholds for PASDAS and DAPSA scores. A total of 229 patients (58.5% male, mean age 55.5 years, mean disease duration 17.1 years) were recruited. The PASS threshold for the PASDAS was 3.79 [area under the curve (AUC) 0.86, sensitivity 0.75, specificity 0.82] and for the DAPSA was 11.10 (AUC 0.91, sensitivity 0.89, specificity 0.82). With the PASDAS, 90% of patients defined as having low disease activity considered their symptom state acceptable, compared with 55% and 17% among those with moderate and high disease activity, respectively. With the DAPSA, 98% of patients in disease remission considered their symptom state acceptable compared with 85, 22 and 18% among those with low, moderate and high disease activity, respectively. We have defined PASS thresholds for PASDAS and DAPSA. The PASDAS target for low disease activity and DAPSA targets of low disease activity or remission align well with PASS.

IntroductionSome retrospective data sources, such as electronic health records in the USA, report composite outcome measures not fully validated in psoriatic arthritis (PsA). However, they often contain global assessments, such as a Physician Global Assessment (PhGA) and Patient Global Assessment (PatGA), along with patient-reported pain scores, which individually are considered validated in PsA. This research described the performance characteristics of a 3-item global assessment and pain (GAP) composite endpoint using data from the ixekizumab phase 3 PsA clinical trial program.MethodsDiscrimination of GAP was assessed by comparing placebo to active treatment arms. The magnitude of treatment effect and responsiveness were compared to Disease Activity Index for PsA (DAPSA), clinical DAPSA, DAPSA28, and Psoriatic Arthritis Disease Activity Score (PASDAS) using effect size (ES) and standardized response mean (SRM), respectively. Construct validity was evaluated through correlation among the composite endpoints, and with other physician- and patient-reported outcomes. Change in GAP was compared in patients who reached low disease activity (LDA) levels based on DAPSA, cDAPSA, and PASDAS vs those who did not.ResultsGAP discriminated between active treatment and placebo with statistically significant separation as early as week 1. The largest ES/SRM was seen with GAP (2.29/1.74) and PASDAS (2.47/1.68). GAP had the strongest correlation with PASDAS (0.81–0.92) and showed moderate correlations with patient-assessed physical function, low correlations with physician-assessed skin and nail psoriasis, and low to moderate correlation with physician-assessed enthesitis. A significantly greater improvement in GAP was seen in the groups achieving LDA states compared to those not (p < 0.001).ConclusionThe GAP composite, an abbreviated endpoint comprising measures common in electronic health records, has promising performance characteristics and could be used to address important clinical questions regarding outcomes and impact of PsA in existing datasets.ClinTrials.gov IdentifierNCT01695239; NCT02349295.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-024-00690-1.

In a complex disease such as psoriatic arthritis (PsA), several methods are available to define remission or low disease activity (LDA), including the assessment of different clinical features. The aim of this study was to compare the composite indices tailored for PsA in patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and biological DMARD (bDMARD). Patients with PsA classified with the ClASsification criteria for Psoriatic ARthritis criteria and with > 6 months followup treated with first csDMARD and bDMARD were consecutively enrolled. To assess disease activity, composite indices tailored for PsA were used, such as the Disease Activity Index for Psoriatic Arthritis (DAPSA), clinical DAPSA (cDAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA) 5/7, and MDA 7/7. DAPSA and cDAPSA score ≤ 4, MDA 7/7, and PASDAS ≤ 1.9 identified remission. MDA 5/7, DAPSA score ≤ 14, cDAPSA score ≤ 13, and PASDAS < 3.2 identified the MDA and LDA criteria. One hundred nine patients with PsA were enrolled: 79 patients were receiving stable treatment with bDMARD and 30 with csDMARD. Overall, 28 (25.6%), 23 (21.1%), 19 (17.4%), and 13 patients (11.9%) were in cDAPSA remission, DAPSA remission, MDA 7/7, and PASDAS ≤ 1.9, respectively. Moreover, 54 (49.5%), 80 (73.3%), 79 (72.3%), and 38 patients (34.8%) were in MDA 5/7, DAPSA LDA, cDAPSA LDA, and PASDAS LDA. Patients treated with bDMARD had significantly lower median DAPSA, cDAPSA, and PASDAS score than patients treated with csDMARD. Patients with PsA receiving bDMARD are more likely to achieve a status of MDA and remission when compared with csDMARD. PASDAS ≤ 1.9 and MDA 7/7 seem to be stringent remission criteria.

Background Optimal treatment regimens and measuring outcomes in psoriatic arthritis (PsA) remain key areas of research. Objectives To examine methotrexate (MTX) and etanercept (ETN) as monotherapy or in combination in a randomized trial and assess the relative performance of PsA-specific composite measures using trial efficacy data. Methods Patients with active PsA naive to biologic drugs (no prior MTX for PsA) were randomized to 3 groups for 48 weeks: ETN 50mg+MTX 20mg weekly (Combo; N=283); ETN 50mg+placebo weekly (ETN-mono; N=284); or MTX 20mg+placebo weekly (MTX-mono; N=284). At week 24, the American College of Rheumatology (ACR)20 and Minimal Disease Activity (MDA) responses were the primary and key secondary endpoints, respectively. Other PsA-specific composite measures used for disease activity included the Psoriatic Arthritis Disease Activity Score (PASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA). Results Baseline characteristics were well balanced in the 3 arms. Mean (SD) age was 48.4 (13.1) years and mean/median PsA duration 3.2/0.6 years. ACR20 and MDA responses at week 24 were significantly greater with ETN-mono vs MTX-mono and Combo vs MTX-mono; ETN-mono and Combo had similar results (Table). PASDAS also showed differences between each ETN-containing arm vs MTX-mono and no difference for ETN-mono vs Combo, whereas study arm differences were not seen with DAPSA. PASDAS had a greater effect size and standardized response than DAPSA. Conclusion In this large randomized, controlled PsA trial, ETN-mono or Combo had greater efficacy than MTX-mono. Combining ETN and MTX did not improve ETN efficacy. Compared with the joint-focused DAPSA, PASDAS captured a wider range of PsA manifestations and performed better in this trial. Disclosure of Interests: Philip J Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: AbbVie, Amgen, BMS, Galapagos, Gilead Sciences, Inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Dafna D Gladman Grant/research support from: AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, David Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc., Christopher T. Ritchlin Grant/research support from: AbbVie, Amgen, UCB Pharma, Consultant for: AbbVie, Amgen, Lilly, Novartis, Pfizer, UCB Pharma, Philip Helliwell Grant/research support from: Paid to charity: from AbbVie, Janssen and Novartis, Consultant for: Paid to charity: from AbbVie, Amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, Laura C Coates Grant/research support from: AbbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead Sciences Inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Vibeke Strand Consultant for: AbbVie, Amgen, Bayer, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kezar, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Servier, UCB., Lyrica Liu Shareholder of: Amgen Inc., Employee of: Amgen Inc., Greg Kricorian Shareholder of: Amgen Inc., Employee of: Amgen Inc., James Chung Shareholder of: Amgen Inc., Employee of: Amgen Inc.

BackgroundThe Phase 3b COSMOS study (NCT03796858) demonstrated the efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit inhibitor, in patients (pts) with psoriatic arthritis (PsA) who had inadequate response...

FRI0333 ACHIEVEMENT OF VERY LOW DISEASE ACTIVITY AND REMISSION TREATMENT TARGETS IS ASSOCIATED WITH REDUCED RADIOGRAPHIC PROGRESSION IN PATIENTS WITH PSORIATIC ARTHRITIS TREATED WITH CERTOLIZUMAB PEGOL

<h3>Background:</h3> Psoriatic arthritis Disease activity Score (PASDAS),¹Disease activity index for Psoriatic arthritis (DAPSA),² and the minimal disease activity (MDA) criteria³ are instruments recommended for evaluating disease activity (DA) in psoriatic arthritis (PsA). RAPID-PsA demonstrated the sustained efficacy of certolizumab pegol (CZP) across the spectrum of PsA symptoms.⁴ a substantial proportion of patients (pts) completing 4 years’ treatment achieved DA targets; ∼75% reached DAPSA low DA (LDA) or remission (REM), and almost 60% had MDA (≥5/7 MDA criteria), half of whom also achieved very low DA (VLDA) (7/7 MDA criteria).⁵ <h3>Objectives:</h3> To report the proportion of pts who achieved PASDAS VLDA and LDA over 216 weeks’ (wks’) CZP treatment, and the overlap in pts achieving PASDAS, DAPSA and MDA. <h3>Methods:</h3> RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to Wk24, dose-blind to Wk48, and open-label (OL) to Wk216.⁵ Outcomes reported for pts randomised to CZP at Wk0 (200 mg every 2 wks or 400 mg every 4 wks, following a 400 mg loading dose at Wks0/2/4) are PASDAS change from baseline (CFB); pts achieving PASDAS LDA (&gt;1.9−&lt;3.2), PASDAS VLDA (≤1.9), DAPSA LDA (&gt;4−≤14), DAPSA REM (≤4), MDA and VLDA to Wk216; and the overlap in pts achieving PASDAS VLDA, DAPSA REM, and VLDA, at Wk216. Data are summarized for observed cases per visit. Pts withdrawing between scheduled visits had their final assessment values assigned to the next scheduled visit timepoint. <h3>Results:</h3> Of 409 pts randomised, 273 received CZP from Wk0, of whom 248 (90.8%) completed Wk24 and 183 (67.0%) completed Wk216. The mean (SD) baseline PASDAS was 6.0 (1.0): in the high DA range, CFB at Wk216 was −3.4 (1.5). Of pts completing Wk216, 66.3% (118/178) were in PASDAS LDA or VLDA (PASDAS VLDA: 36.5% [n=65]): less than the proportion reaching DAPSA LDA or REM (76.2%), but more than those achieving MDA or VLDA (57.8%) (Figure a). At Wk216, of pts achieving PASDAS VLDA, a large proportion (71% [46/65]) had VLDA based on MDA criteria (<b>Figure B1</b>) and most (94% [61/65]) achieved DAPSA REM (<b>Figure B2</b>). Almost all pts achieving VLDA (96.1% [50/52]) were also in DAPSA REM (<b>Figure B3</b>). After 4 years’ CZP treatment, 25.8% (46/178) pts achieved the PASDAS VLDA, DAPSA REM and VLDA. <h3>Conclusion:</h3> A substantial proportion of pts completing 4 years’ CZP treatment achieved PASDAS LDA or VLDA, and the vast majority who achieved PASDAS VLDA at Wk216 also reached DAPSA REM and/or VLDA. 1 in 4 pts achieved the most stringent DA target with all 3 instruments. <h3>References</h3> [1] Helliwell P. Ann Rheum Dis2013;72:986–91; 2. Schoels M. Ann Rheum Dis 2016;75:811–18; 3. Coates L. Ann Rheum Dis2010;69:48–53; 4. van der Heijde D. RMD Open 2018;4:e000582. <h3>Acknowledgement:</h3> We thank the patients who participated. This study was funded by UCB Pharma, medical writing by Hinal Tanna, Costello Medical, UK. <h3>Disclosure of interests:</h3> Laura C Coates Grant/research support from: abbVie, Celgene, Lilly, Novartis and Pfizer, Consultant for: abbVie, amgen, BMS, Celgene, Galapagos, Gilead Sciences inc., Janssen, Lilly, Novartis, Pfizer, Prothena Corp and UCB, Joseph F. Merola Consultant for: Biogen IDEC, abbvie, amgen, Eli Lilly and Company, Novartis, Pfizer, Janssen, UCB, Samumed, Celgene, Sanofi Regeneron, Merck, and GSK, Oliver FitzGerald: None declared, arthur Kavanaugh Grant/research support from: UCB Pharma, alice B Gottlieb Grant/research support from: PI: incyte Corporation, Janssen-Ortho inc., Lilly ICOS LLC, Novartis, UCB, XBiotech, Consultant for: abbVie, Dermira, incyte Corporation, Lilly ICOS LLC, Novartis, Sun Pharmaceutical industries Ltd., avotres (unpaid), XBiotech (unpaid), Speakers bureau: abbVie, Eli Lilly and Company, Janssen Biotech; advisory board: Bristol-Myers Squibb, Celgene Corporation, Janssen Biotech, Janssen-Ortho inc., LEO Pharma, Novartis, UCB, William Tillett Grant/research support from: abbVie, Celgene, and Lilly, Consultant for: abbVie, Celgene, Lilly, Novartis, and Pfizer, Speakers bureau: abbvie, Celgene, Lilly, Janssen, Novartis, UCB, and Pfizer, Lars Bauer Employee of: Employee of UCB Pharma, Bengt Hoepken Employee of: Employee of UCB Pharma, Tommi Nurminen Employee of: Employee of UCB Pharma, Philip J Mease Grant/research support from: abbVie, amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Consultant for: abbVie, amgen, BMS, Galapagos, Gilead Sciences, inc., Janssen, Lilly, Novartis, Pfizer, SUN and UCB, Speakers bureau: abbVie, amgen, BMS, Celgene, Genentech, Janssen, Lilly, Novartis, Pfizer and UCB, Philip Helliwell Grant/research support from: Paid to charity: from abbVie, Janssen and Novartis, Consultant for: Paid to charity: from abbVie, amgen, Pfizer, and UCB and Celgene. Paid to self: from Celgene and Galapagos, Désirée van der Heijde Consultant for: abbVie, amgen, astellas, astraZeneca, Bristol-Myers Squibb, Boehringer ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Union Chimique Belge

ObjectivesTo compare responsiveness and longitudinal validity of Disease Activity Score 28 (DAS28), Disease Activity index for PSoriatic Arthritis (DAPSA), Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), GRAppa Composite scorE (GRACE) and Minimal Disease Activity (MDA) in usual care PsA patients, within 1 year after diagnosis.MethodsData collected in the Dutch southwest early PsA cohort (DEPAR) were used. Responsiveness was assessed using effect size (ES), standardized response mean (SRM), and discrimination between different general health states. Longitudinal validity was tested using mixed models with outcomes health-related quality of life (HRQOL), productivity and disability.ResultsResponsiveness was highest for PASDAS, with ES 1.00 and SRM 0.95, lowest for DAPSA, with ES 0.73 and SRM 0.71, and in between for DAS28, CPDAI and GRACE. Differences in general health were best discriminated with PASDAS and GRACE. Patients reporting stable or worsening general health could not be distinguished by DAS28 or CPDAI. Discrimination was better using DAPSA, but worse than when using PASDAS and GRACE. Longitudinal evolvement of HRQOL and productivity had the highest association with low disease activity according to GRACE, followed by PASDAS, MDA, DAPSA, DAS28, with the lowest association for CPDAI.ConclusionPASDAS and GRACE were superior with respect to responsiveness, and together with MDA best related to longitudinal evolvement of HRQOL, productivity and disability. Responsiveness and longitudinal validity of most outcomes were inferior for DAS28, DAPSA and CPDAI. As alternatives to the continuous measure DAPSA, use of PASDAS or GRACE should be considered.

AB0753 COMPARING COMPOSITE MEASURES OF DISEASE ACTIVITY IN PSORIATIC ARTHRITIS: RESULTS FROM A RANDOMIZED PHASE 2 TRIAL WITH GUSELKUMAB

Objective: To determine whether a family history of spondyloarthritis (SpA) is associated with clinical presentation at the start of tumour necrosis factor inhibitor (TNFi) treatment, or predictive of TNFi drug survival and treatment response in patients with SpA. Method: Family history of SpA in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and undifferentiated SpA (uSpA) from the Swedish Rheumatology Quality register starting a TNFi as their first biologic in 2006–2018 was assessed through national registers. Clinical characteristics at treatment start were compared by family history status. We used Cox regression to estimate hazard ratios for drug discontinuation, and analysed treatment response at 3 and 12 months with linear regression. Multiple imputation was used to address missing data. Results: We included 9608 patients. Patients with family history had an earlier age at onset and longer disease duration at TNFi treatment start, but did not differ regarding disease activity and presence of SpA manifestations. Hazard ratios for drug discontinuation were 1.08 [95% confidence interval (CI) 0.89–1.31] for AS patients with a family history of AS, 1.02 (95% CI 0.89–1.18) for PsA patients with a family history of PsA, and 1.11 (95% CI 0.85–1.45) for uSpA patients with a family history of uSpA, after adjusting for demographic, socioeconomic, and SpA-related factors. Treatment response at 3 and 12 months was similar between groups. Conclusion: Family history of SpA was not found to be associated with clinical presentation at the start of TNFi treatment, nor was it associated with drug survival or treatment response in SpA patients starting a first TNFi.

AB0742 ACHIEVEMENT OF PASDAS LOW DISEASE ACTIVITY AND VERY LOW DISEASE ACTIVITY IN PATIENTS WITH PSORIATIC ARTHRITIS TREATED WITH CERTOLIZUMAB PEGOL OVER 4 YEARS AND THE OVERLAP WITH DAPSA AND MDA DISEASE ACTIVITY TARGETS

ObjectiveWe used the Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) data set to examine the impact of presence of enthesitis, dactylitis,...

POS1021 THE PsABio STUDY IN ITALY: A REAL-WORLD COMPARISON OF THE PERSISTENCE, EFFECTIVENESS AND SAFETY OF USTEKINUMAB AND TUMOUR NECROSIS FACTOR INHIBITORS IN PATIENTS WITH PSORIATIC ARTHRITIS

SAT0295 Comparison of Composite Measures of Disease Activity in Psoriatic Arthritis Using Data from an Interventional Study with Golimumab.