1017: Minimal Important Difference (MID), Minimal Detectable Change (MDC), and Disease Activity Thresholds for Two Novel Composite Instruments (3VAS, 4VAS) in Patients with Psoriatic Arthritis: Pooled Analysis of Three Phase 3 Studies

William Tillett¹, Laura Coates², Marijn Vis³, Joseph Merola⁴, Enrique R Soriano⁵, Michelle Perate⁶, May Shawi⁷, Miriam Zimmermann⁸, Emmanouil Rampakakis⁹, Mohamed Sharaf¹⁰, Peter Nash¹¹ and Philip Helliwell¹², ¹Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom, ²Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK, Oxford, England, United Kingdom, ³Erasmus MC Universitair Medisch Centrum, Rotterdam, Netherlands, ⁴Harvard Medical School, Brigham and Women's Hospital, Boston, MA, ⁵Rheumatology Unit and University Institute, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, ⁶Janssen Scientific Affairs, LLC, Horsham, PA, ⁷Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, ⁸Immunology, Janssen Scientific Affairs, LLC, Zug, Switzerland, ⁹McGill University, Department of Pediatrics and JSS Medical Research, Montréal, QC, Canada, ¹⁰Johnson & Johnson, Middle East FZ LLC, Dubai, United Arab Emirates, ¹¹School of Medicine, Griffith University, Sunshine Coast, Australia, ¹²Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom

Background/Purpose: Though continuous composite measures of disease activity for psoriatic arthritis (PsA) assessment exist, abbreviated measures that are more feasible for screening in routine clinical practice are needed. The 3 Visual Analogue Scale (VAS) and 4 VAS scores were developed by abridging the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Exercise (GRACE) measure to be the first short multidimensional composite measures specifically for use in PsA routine clinical care. The measures were shown to have superior performance than several established composite measures using small datasets,¹. GRAPPA members recommended further testing of 3VAS/4VAS in observational and trial datasets.

Methods: This post-hoc analysis of the DISCOVER 1/2 and COSMOS studies^2-4 used pooled data through week (W) 24 from all treatment groups across studies. The correlation of 3VAS/4VAS with DAPSA, PASDAS, physician global assessment (PhGA), and patient GA (PtGA) was assessed with Pearson's correlation coefficient. Minimal Important Difference (MID) was assessed with 4 distribution-based methods (based on standard error of the measurement, effect size, reliable change index [RCI], and RCI_diff). Minimal detectable change (MDC) was assessed with the standard formula (Table 2). Clinically relevant thresholds for low, moderate and high disease activity were estimated with receiver operating characteristic analysis and DAPSA (≤4, >4-≤14, >14-≤28, >28), PASDAS (≤1.9, >1.9-≤3.2, >3.2-< 5.4, ≥5.4), and PhGA/PtGA (≤1, >1-≤3, >3-≤6, >6 cm) as anchors.

Results: 1,405 pts were included, of whom 51.3% were male, with a mean (SD) age of 47.1 (11.8), and PsA duration of 6.4 (6.5) years. At BL, the mean (SD) 3VAS, 4VAS, DAPSA, PASDAS, PhGA, and PtGA scores of 6.4 (1.6), 6.3 (1.6), 45.8 (20.2), 6.5 (1.1), 6.5 (1.6), and 6.7 (2.0), respectively, reflected high levels of disease activity. Through W24, both 3VAS and 4VAS showed very strong correlation with PtGA (r_3VAS=0.92, r_4VAS=0.94) and PASDAS (r_3VAS=0.81, r_4VAS=0.82), strong with PhGA (r_3VAS=0.77, r_4VAS=0.74), and moderate to strong with DAPSA (r_3VAS=0.59, r_4VAS=0.61). Calculated MIDs were 0.9 (range: 0.7-1.3 across methodologies) for 3VAS and 0.9 (range: 0.6-1.3) for 4VAS (Table 1). MDC estimates were 3.3 (range 2.1-4.2 across follow-up intervals) for 3VAS and 3.2 (range: 2-4) for 4VAS (Table 2). Cut-off values for low, moderate and high disease activity were 2.0, 3.4, and 4.9 for 3VAS and 2.1, 3.5 and 5.1 for 4VAS (Figure).

Conclusion: Using a large pooled clinical trial dataset of pts with active PsA, we have calculated clinically relevant thresholds for improvement, as well as disease activity thresholds, for 3VAS and 4VAS. These estimates are generally comparable to those previously reported⁵ and can be used to set treatment targets as well as screen disease activity in routine care when resources are limited or during remote pt monitoring.

References

Tillett W et al. J Rheum. 2021 Mar 1;jrheum.201675

Deodhar A et al. Lancet. 2020 Apr 4;395(10230):1115

Mease PJ et al. Lancet. 2020 Apr 4;395(10230):1126

Coates LC et al. Ann Rheum Dis. 2022;81(3):359

Tillett W et al. Ann Rheum Dis. 2021;80:135

Table 1. Minimally Important Difference (MID) for 3VAS, 4VAS, DAPSA, PASDAS, PhGA, and PtGA

Table 2. Minimal Detectable Change (MDC) for 3VAS, 4VAS, DAPSA, PASDAS, PhGA, and PtGA

Table 3. Disease Activity Thresholds for 3VAS & 4VAS
Disclosures: W. Tillett, AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, UCB; L. Coates, AbbVie, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb (BMS), Eli Lilly, Gilead, Galapagos, Janssen, Medac, Novartis, Pfizer, UCB, Celgene, Biogen, Moonlake, GlaxoSmithKlein (GSK); M. Vis, AbbVie/Abbott, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB, the Dutch Arthritis Foundation; J. Merola, AbbVie, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, UCB Pharma, Arena, Avotres, EMD, LEO Pharma, Merck, Regeneron, Sanofi; E. Soriano, AbbVie, Amgen, Bristol-Myers Squibb(BMS), Eli Lilly, Janssen, Novartis, Pfizer, UCB, Roche; M. Perate, Janssen Pharmaceutical Companies of Johnson and Johnson; M. Shawi, Janssen Pharmaceutical Companies of Johnson and Johnson; M. Zimmermann, Janssen Scientific Affairs, LLC, Johnson & Johnson; E. Rampakakis, Janssen, JSS Medical Research; M. Sharaf, Janssen Pharmaceutical Companies of Johnson and Johnson; P. Nash, AbbVie, Eli Lilly, Janssen, Gilead, Bristol-Myers Squibb (BMS), Celgene; P. Helliwell, Eli Lilly, AbbVie, Amgen, Janssen, Novartis.