Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib

Abstract

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

Methods: This post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson's Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients.

Results: Across csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients.

Conclusions: This analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients' perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care.

Trial registration: Clinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009).

Keywords: Disability; Fatigue; Pain; Patient Global Assessment; Patient-reported outcomes; Physical function; Rheumatoid arthritis; Tofacitinib.

Conflict of interest statement

VS has received consulting fees or other remuneration from AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB.

JK has participated in speakers’ bureaus and has consulted for Pfizer Inc.

RA has received research grants and speakers’ honoraria from Pfizer Inc.

GW was an employee and shareholder of Pfizer Inc at the time of the analysis.

AD, HS, RG, and CWM are employees of Pfizer Inc and own stock or stock options in Pfizer Inc.

Figures

Fig. 1

Associations between LDA and Pain, HAQ-DI, and FACIT-F outcomes at month 3 in csDMARD-IR patients. Proportions of csDMARD-IR patients at month 3 who did/did not report a mild Pain (VAS score ≤ 20 mm), b moderate improvements in Pain (≥ 30% decreases from baseline), c substantial improvements in Pain (≥ 50% decreases from baseline), d HAQ-DI scores ≥ normative values (≤ 0.25), or e FACIT-F scores ≥ normative values (≥ 43.5), stratified by LDA status (PtGA VAS score ≤ 20 mm). Denominators represent the number of patients who did/did not report LDA, respectively. Abbreviations: BID twice daily, CI confidence interval, csDMARD conventional synthetic disease-modifying antirheumatic drug, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire-Disability Index, IR inadequate responder, LDA low disease activity, PtGA Patient Global Assessment of Disease Activity, VAS Visual Analog Scale

Fig. 2

Associations between moderate improvements in PtGA and Pain, HAQ-DI, and FACIT-F outcomes at month 3 in csDMARD-IR patients. Proportions of csDMARD-IR patients at month 3 who did/did not report a mild Pain (VAS score ≤ 20 mm), b moderate improvements in Pain (≥ 30% decreases from baseline), c substantial improvements in Pain (≥ 50% decreases from baseline), d HAQ-DI scores ≥ normative values (≤ 0.25), or e FACIT-F scores ≥ normative values (≥ 43.5), stratified by reporting of moderate improvements in PtGA (≥ 30% decreases from baseline). Denominators represent the number of patients who did/did not report moderate PtGA improvements, respectively. Abbreviations: BID twice daily, CI confidence interval, csDMARD conventional synthetic disease-modifying antirheumatic drug, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire-Disability Index, IR inadequate responder, PtGA Patient Global Assessment of Disease Activity, VAS Visual Analog Scale

Fig. 3

Associations between substantial improvements in PtGA and Pain, HAQ-DI, and FACIT-F outcomes at month 3 in csDMARD-IR patients. Proportions of csDMARD-IR patients at month 3 who did/did not report a mild Pain (VAS score ≤ 20 mm), b moderate improvements in Pain (≥ 30% decreases from baseline), c substantial improvements in Pain (≥ 50% decreases from baseline), d HAQ-DI scores ≥ normative values (≤ 0.25), or e FACIT-F scores ≥ normative values (≥ 43.5), stratified by reporting of substantial improvements in PtGA (≥ 50% decreases from baseline). Denominators represent the number of patients who did/did not report substantial PtGA improvements, respectively. Abbreviations: BID twice daily, CI confidence interval, csDMARD conventional synthetic disease-modifying antirheumatic drug, FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue, HAQ-DI Health Assessment Questionnaire-Disability Index, IR inadequate responder, PtGA Patient Global Assessment of Disease Activity, VAS Visual Analog Scale