Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis

Abstract

Background: In rheumatoid arthritis (RA), little is known about clinical responses to treatment as predictors of patient-reported outcome (PRO) changes. In this post hoc analysis, we examined the relationship between clinical outcomes at week 12 and PRO changes at week 24 in patients with RA.

Methods: In an open-label study, Latin American patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX) were randomized to receive etanercept 50 mg/week plus MTX (ETN+MTX; n=281) or an additional conventional disease-modifying anti-rheumatic drug (DMARD) plus MTX (DMARD+MTX; n=142) for 24 weeks. The PROs included Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form (SF-36), Physician and Patient Global Assessment scores (PGA, PtGA), Physician and Patient Satisfaction, and an activity impairment assessment. PRO changes at week 24 were calculated by week-12 improvements using the American College of Rheumatology criteria (ACR <20, ≥20 to <50, ≥50 to <70, and ≥70) and the 28-joint Disease Activity Scores (DAS28 ≥3.2, ≥2.6 to <3.2, and <2.6). Observed-cases data were analyzed using an ANCOVA model with linear contrast, adjusted for baseline PRO and ACR/DAS28 values.

Results: For both ETN+MTX- and DMARD+MTX-treated patients, there was a significant linear trend between week-12 changes in ACR and DAS28 responses and week-24 changes in HAQ-DI (P<0.001 for all), with numerical improvements generally favoring ETN+MTX. Similar relationships were observed for SF-36, PGA, PtGA, Physician Satisfaction, Patient Satisfaction, and activity impairment.

Conclusions: In patients with RA, clinical response after 12 weeks of treatment with ETN+MTX or DMARD+MTX could be a predictor of week-24 response for several PROs.

Trial registration: ClinicalTrials.gov, NCT00848354.

Keywords: clinical outcome; etanercept; patient-reported outcome; predictor; rheumatoid arthritis.

Conflict of interest statement

GGB: Consultant for Janssen. Speaker for Janssen, Pfizer, and Roche. RMX: Consultant for AbbVie, Janssen, Lilly, and Pfizer. Speaker for AbbVie, BMS, Janssen, Lilly, Novartis, Pfizer, and Roche. RMX also reports personal fees from Abbvie, Pfizer, UCB, Lilly, and Roche, outside the submitted work. MdlV: Consultant and speaker for Pfizer, Sanofi, and Raffo. Speaker for Abbvie, BMS, Janssen, and Lilly. Participant in educational programs supported by Roche. JASC: Received sponsorship from Roche to attend an educational event. GS, CB, and BV are Pfizer employees and may own company stock. RDP was a Pfizer employee during the development of the manuscript and may own company stock. The authors report no other conflicts of interest in this work.

© 2019 Guerra Bautista et al.

Figures

Figure 1

(A–D) Relationship between HAQ-DI and SF-36 PCS and clinical response. Notes: Numerals in each column denote the numbers of participants. P-values are from ANCOVA linear trend contrast within each treatment. Abbreviations: ACR, American College of Rheumatology (response criteria); ANCOVA, analysis of covariance; CI, confidence interval; DAS28, 28-joint Disease Activity Scale (response criteria); DMARD, disease-modifying anti-rheumatic drug; ETN, etanercept; HAQ-DI, Health Assessment Questionnaire Disability Index; SF-36 PCS, Short Form 36, Physical Component Summary.

Figure 2

(A–D) Relationship between HADS subscales and clinical response. Notes: Numerals in each column denote the numbers of participants. P-values are from ANCOVA linear trend contrast within each treatment. Abbreviations: ACR, American College of Rheumatology (response criteria); ANCOVA, analysis of covariance; CI, confidence interval; DAS28, 28-joint Disease Activity Scale (response criteria); DMARD, disease-modifying anti-rheumatic drug; ETN, etanercept; HADS-A, Hospital Anxiety and Depression Scales subscale for anxiety; HADS-A, Hospital Anxiety and Depression Scales subscale for anxiety.

Figure 3

(A–D) Relationship between PGA/PtGA and clinical response. Notes: Numerals in each column denote the numbers of participants. P-values are from ANCOVA linear trend contrast within each treatment. Abbreviations: ACR, American College of Rheumatology (response criteria); ANCOVA, analysis of covariance; CI, confidence interval; DAS28, 28-joint Disease Activity Scale (response criteria); DMARD, disease-modifying anti-rheumatic drug; ETN, etanercept; PGA, Physician Global Assessment; PtGA, Patient Global Assessment.

Figure 4

(A–D) Satisfaction with treatment and clinical response. Note: Numerals in each column denote the numbers of participants. P-values are from ANCOVA linear trend contrast within each treatment. Abbreviations: ACR, American College of Rheumatology (response criteria); ANCOVA, analysis of covariance; CI, confidence interval; DAS28, 28-joint Disease Activity Scale (response criteria); DMARD, disease-modifying anti-rheumatic drug; ETN, etanercept; PGA, Physician Global Assessment; PtGA, Patient Global Assessment.