Dataset Information

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).

SUBMITTER: Strand V

PROVIDER: S-EPMC7566034 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Strand Vibeke V Kaine Jeffrey J Alten Rieke R Wallenstein Gene G Diehl Annette A Shi Harry H Germino Rebecca R Murray Christopher W CW

Arthritis research & therapy 20201015 1

<h4>Background</h4>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).<h4>Methods</h4>This post hoc analysis used data pooled from three ...[more]

PMID: 33059710

Similar Datasets

Project description:BackgroundThe detection of statistically significant reductions in radiographic progression during clinical studies in patients with rheumatoid arthritis (RA) has become increasingly difficult over the past decade due to early-escape study designs and declining rates of progression in control-group patients. We investigated the impact of extremes of radiographic data (outliers) and baseline prognostic factors on detection of treatment effects, to provide guidance on future analysis of joint structural data in RA clinical trials.MethodsData were from two, phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib in adult patients with moderate to severe RA: ORAL Scan (NCT00847613) and ORAL Start (NCT01039688). These studies detected significant reductions in radiographic progression with tofacitinib 10 mg twice daily (BID) plus background methotrexate (ORAL Scan), and with tofacitinib 5 or 10 mg BID as monotherapy (ORAL Start). We evaluated mean changes from baseline in van der Heijde modified total Sharp score (mTSS) at month 6 and month 12, using analysis of covariance (ANCOVA). A trimmed analysis was used to deal with extremes of data. The impact of baseline prognostic factors on radiographic progression was evaluated using ANCOVA to analyze the mean change from baseline in mTSS for each factor in turn.ResultsThe analysis included data from 720 patients from ORAL Scan and 880 patients from ORAL Start. Trimmed analyses were unbiased for the true mean estimate and enabled us to remove the effect of influential extreme observations in the data set. Almost all patients had at least one poor prognostic factor at baseline (e.g., high level of disease activity, or positive for rheumatoid factor). The strongest predictor of treatment effect was the severity of radiographic damage at baseline.ConclusionsA trimmed analysis can establish whether any significant inhibition of structural damage is being driven by extremes of data, and should be one of the sensitivity analyses of choice for structural data in RA clinical trials. Furthermore, analysis of radiographic data based on baseline prognostic factors may reveal increased treatment effects. Application of these methods to analysis of radiographic data from clinical trials in patients with RA, allows a more complete interpretation of data.Trial registrationClinicaltrials.gov NCT00847613 (registered 17 February 2009) and NCT01039688 (registered 23 December 2009).

Project description:BackgroundPreclinical data suggest that tofacitinib would protect bone health in patients with rheumatoid arthritis (RA).ObjectiveTo assess fracture risk in tofacitinib RA clinical trials.DesignPost hoc analysis.MethodsWe analyzed pooled data of phase I/II/III and long-term extension studies ('P123LTE cohort'), pooled data of placebo-controlled portions of phase III studies (phase III placebo-controlled cohort), and data from ORAL Surveillance [phase IIIb/IV randomized, open-label trial evaluating tofacitinib 5/10 mg twice daily (BID) vs tumor necrosis factor inhibitor (TNFi) in patients ⩾ 50 years with ⩾ 1 additional cardiovascular risk factor].ResultsIn the phase III placebo-controlled cohort, incidence rates (IRs) [95% confidence interval (CI)] of fracture were 2.11 (1.09-3.68), 2.56 (1.23-4.71), and 4.43 (1.78-9.12) per 100 patient-years (PYs) for tofacitinib 5 mg BID, tofacitinib 10 mg BID, and placebo, respectively [tofacitinib 5 mg BID vs placebo: hazard ratio (HR) (95% CI) = 0.55(0.18-1.65); tofacitinib 10 mg BID vs placebo: HR (95% CI) = 0.72 (0.26-2.01)]. In P123LTE, IRs (95% CI) were 2.62 (2.29-2.99) and 2.26 (2.02-2.52) per 100 PY for average tofacitinib 5 and 10 mg BID, respectively. In ORAL Surveillance, IRs (95% CI) were 2.79 (2.34-3.30), 2.87 (2.40-3.40), and 2.27 (1.87-2.74) per 100 PY for tofacitinib 5 mg BID, tofacitinib 10 mg BID, and TNFi, respectively. In ORAL Surveillance, the risk of fracture was numerically higher than TNFi for tofacitinib 5 mg BID [HR (95% CI) = 1.23 (0.96-1.58)] and tofacitinib 10 mg BID [HR (95% CI) = 1.26 (0.97-1.62)]. In ORAL Surveillance, independent predictors of all and osteoporotic fractures with tofacitinib or TNFi included age ⩾ 65, female sex, history of fracture/osteoporosis, and baseline oral corticosteroid use.ConclusionThis post hoc analysis showed numerically lower fracture risk with tofacitinib versus placebo and numerically greater risk versus TNFi. We did not identify any tofacitinib-specific predictors of fractures, and predictors of fracture were generally aligned with prior literature in the general population and patients with RA. Patients with fracture risk factors should be adequately monitored and treated.Clinical trial registrationNCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02187055, NCT02831855, NCT00413699, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00661661, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT01262118, NCT01484561, NCT02281552, NCT02147587, NCT02092467.

Dataset Information

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.

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets