Relationships between psoriatic arthritis composite measures of disease activity with patient-reported outcomes in phase 3 studies of tofacitinib

Laura C Coates, Andrew G Bushmakin, Oliver FitzGerald, Dafna D Gladman, Lara Fallon, Joseph C Cappelleri, Ming-Ann Hsu, Philip S Helliwell, Laura C Coates, Andrew G Bushmakin, Oliver FitzGerald, Dafna D Gladman, Lara Fallon, Joseph C Cappelleri, Ming-Ann Hsu, Philip S Helliwell

Abstract

Background: In psoriatic arthritis (PsA), further understanding of the relationships between clinical measures and patient-reported outcomes (PROs) is needed. This post hoc analysis evaluated associations between minimal disease activity (MDA) as a continuous outcome (termed ScoreMDA) or Psoriatic Arthritis Disease Activity Score (PASDAS) with selected PROs not included in the composite measures.

Methods: Data from two phase 3 studies of tofacitinib in PsA (OPAL Broaden [NCT01877668; N = 422]; OPAL Beyond [NCT01882439; N = 394]) were included. MDA (binary outcome) was defined as meeting ≥5/7 criteria. For ScoreMDA, each criterion was assigned a value (1 = true; 0 = false; score range, 0-7; scores ≥5 indicated MDA). For PASDAS (score range, 0-10), higher scores indicated worse disease activity. PROs analyzed included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Patient's Assessment of Arthritis Pain visual analog scale (Pain VAS), and EuroQoL-Five Dimensions-Three Level Health Questionnaire visual analog scale (EQ-5D-3L VAS) and utility index. Relationships were evaluated using repeated measures regression models.

Results: Similar, approximately linear relationships were confirmed between PASDAS or ScoreMDA and PROs in both studies. In OPAL Broaden and OPAL Beyond, a one-point difference in PASDAS was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (- 6.7 mm, - 6.9 mm), Pain VAS (9.9 mm, 10.7 mm), and FACIT-F (- 2.8, - 3.3). A one-point difference in ScoreMDA was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (5.0 mm, 5.5 mm) and FACIT-F (1.9, 2.7) in OPAL Broaden and OPAL Beyond, respectively.

Conclusions: Linear associations between PASDAS or ScoreMDA and PROs provide interpretable and quantifiable metrics between composite clinical measures and PROs, highlighting the importance of these measures in understanding the relevance of treat-to-target goals in PsA.

Trial registration: ClinicalTrials.gov, NCT01877668 . Registered on June 12, 2013. ClinicalTrials.gov, NCT01882439 . Registered on June 18, 2013.

Keywords: Minimal disease activity; Patient-reported outcomes; Psoriatic arthritis.

Conflict of interest statement

LCC is funded by a National Institute for Health Research (NIHR) Clinician Scientist award. The research was supported by the NIHR Oxford Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. LCC has also received honoraria and/or research funding from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, and UCB. OF has received research grants from AbbVie, BMS, Eli Lilly, Novartis, and Pfizer Inc; is a consultant for BMS, Celgene, Eli Lilly, Janssen, and Pfizer Inc; and has been on speaker bureaus for AbbVie, Janssen, and Pfizer Inc. DDG has received research grants from AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Pfizer Inc, and UCB, and is a consultant for AbbVie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, and UCB. AGB, LF, JCC, and M-AH are stockholders and employees of Pfizer Inc. PSH has received research grants from AbbVie, Janssen, and Novartis, and is a consultant for AbbVie, Amgen, Celgene, Galapagos, Pfizer Inc, and UCB.

Figures

Fig. 1
Fig. 1
Estimated relationship between PASDAS/Pain VAS (a) and ScoreMDA/SF-36v2 PCS (b). Data from OPAL Broaden (N = 422). SF-36v2 PCS: norm-based scores were used (a score of 50 representing the mean for the general population, with higher scores indicating less impairment); ScoreMDA: continuous MDA with values from 0 to 7 (0–4, no MDA; 5–7, MDA). Arrows indicate the direction of improvement. MDA, minimal disease activity; Pain VAS, Patient’s Assessment of Arthritis Pain visual analog scale; PASDAS, Psoriatic Arthritis Disease Activity Score; PCS, Physical Component Summary; SF-36v2, Short Form-36 Health Survey Version 2, acute
Fig. 2
Fig. 2
Estimated relationships between PASDAS and FACIT-F total score (a), Pain VAS (b), and HAQ-DI (c). Data from OPAL Broaden (N = 422) and OPAL Beyond (N = 394); all treatment groups from each phase 3 study were pooled for analysis. Arrows indicate the direction of improvement. FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; Pain VAS, Patient’s Assessment of Arthritis Pain visual analog scale; PASDAS, Psoriatic Arthritis Disease Activity Score; VAS visual analog scale
Fig. 3
Fig. 3
Estimated relationships between PASDAS and EQ-5D-3L VAS (a) and EQ-5D-3L UI (b). Data from OPAL Broaden (N = 422) and OPAL Beyond (N = 394); all treatment groups from each phase 3 study were pooled for analysis. Arrows indicate the direction of improvement. EQ-5D-3L, EuroQoL-Five Dimensions-Three Level Health Questionnaire; PASDAS, Psoriatic Arthritis Disease Activity Score; UI, utility index; VAS, visual analog scale
Fig. 4
Fig. 4
Estimated relationships between ScoreMDA and FACIT-F total score (a), SF-36v2 PCS (b), EQ-5D-3L VAS (c), and EQ-5D-3L UI (d). Data from OPAL Broaden (N = 422) and OPAL Beyond (N = 394); all treatment groups from each phase 3 study were pooled for analysis. SF-36v2 PCS: norm-based scores were used (a score of 50 representing the mean for the general population, with higher scores indicating less impairment); ScoreMDA: continuous MDA with values from 0 to 7 (0–4, no MDA; 5–7, MDA). EQ-5D-3L, EuroQoL-Five Dimensions-Three Level Health Questionnaire; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; MDA, minimal disease activity; PCS, Physical Component Summary; SF-36v2, Short Form-36 Health Survey Version 2, acute; UI, utility index, VAS, visual analog scale

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