What Makes Patients with Fibromyalgia Feel Better? Correlations Between Patient Global Impression of Improvement and Changes in Clinical Symptoms and Function: A Pooled Analysis of 4 Randomized Placebo-controlled Trials of Duloxetine
To investigate the relationship between changes in clinical rating scale items and endpoint Patient Global Impression of Improvement (PGI-I).
Data were pooled from 4 randomized, double-blind, placebo-controlled studies of duloxetine in patients with fibromyalgia (FM). Variables included in the analyses were those that assessed symptoms in FM domains of pain, fatigue, sleep, cognitive difficulties, emotional well-being, physical function, and impact on daily living. The association of endpoint PGI-I with changes from baseline in individual variables was assessed using Pearson product-moment correlations (r). Stepwise linear regression was used to identify those variables for which changes from baseline were statistically significant independent predictors of the endpoint PGI-I ratings.
Changes in pain variables and interference of symptoms with the ability to work were highly correlated (r >or= 0.5 or r <or= -0.5) with endpoint PGI-I. Moderate correlation with endpoint PGI-I (0.30 <or= r < 0.5 or -0.5 < r <or= -0.30) included changes in variables that assessed physical functioning, depression, anxiety, fatigue, and several variables related to impact on daily living. Independent predictor variables of endpoint PGI-I identified by stepwise linear regression included assessments for pain, physical function, vitality, anxiety, social function, and tender point thresholds.
In addition to pain reduction, what makes patients with FM feel better may include improvement in fatigue, physical functioning, mood, and impact on daily living. An assessment of these domains may be important in clinical trials of FM and in the management of patients with FM.
"A recent analysis of FM responder definitions suggested that inclusion of assessments of symptom and functional domains in addition to pain could significantly improve the ability of clinical trials to identify clinically meaningful improvements . In addition, improvements in fatigue, physical function, and sleep, as well as pain, have individually been shown to correlate well with improvements on the patient global impression of change scale [24, 49–51], which provides an indication of overall patient improvement. "
[Show abstract][Hide abstract] ABSTRACT: Duloxetine, milnacipran, and pregabalin are approved by the United States Food and Drug Administration for the management of fibromyalgia. A number of meta-analyses, pooled analyses, and systematic reviews have been published in recent years involving the efficacy of these three medications for pain in fibromyalgia. Despite being based on the same clinical data, some analyses found these treatments to have a clinically relevant effect on pain, while others concluded that the advantages were small or of questionable clinical relevance. This commentary discussed possible reasons behind these differing conclusions and explored ways of evaluating the clinical relevance of pharmacological treatments for fibromyalgia. In particular, we considered: (1) the importance of judicious and careful interpretation of average treatment effect size and the recognition that average treatment effect sizes do not always tell the whole story; (2) the utility of individual patient response data to assess clinical relevance; and (3) the importance of considering pain reduction within the context of other benefits due to the presence of associated symptoms in patients with fibromyalgia.
"Previous studies have suggested that there is an association between pain and fatigue. For instance, changes in pain and fatigue in patients with fibromyalgia have been found to be moderately correlated with patient ratings of feeling 'better' . In addition, a review of studies in patients with various chronic pain disease states reported that fatigue decreases when pain improves . "
[Show abstract][Hide abstract] ABSTRACT: Fatigue is one of the most disabling symptoms associated with fibromyalgia that greatly impacts quality of life. Fatigue was assessed as a secondary objective in a 2-phase, 24-week study in outpatients with American College of Rheumatology-defined fibromyalgia.
Patients were randomized to duloxetine 60-120 mg/d (N = 263) or placebo (N = 267) for the 12-week acute phase. At Week 12, all placebo-treated patients were switched to double-blind treatment with duloxetine for the extension phase. Fatigue was assessed at baseline and every 4 weeks with the Multidimensional Fatigue Inventory (MFI) scales: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Activity, and Reduced Motivation. Other assessments that may be associated with fatigue included Brief Pain Inventory (BPI) average pain, numerical scales to rate anxiety, depressed mood, bothered by sleep difficulties, and musculoskeletal stiffness. Treatment-emergent fatigue-related events were also assessed. Changes from baseline to Week 12, and from Week 12 to Week 24, were analyzed by mixed-effects model repeated measures analysis.
At Week 12, duloxetine versus placebo significantly (all p < .05) reduced ratings on each MFI scale, BPI pain, anxiety, depressed mood, and stiffness. Improvement in ratings of being bothered by sleep difficulties was significant only at Weeks 4 and 8. At Week 24, mean changes in all measures indicated improvement was maintained for patients who received duloxetine for all 24 weeks (n = 176). Placebo-treated patients switched to duloxetine (n = 187) had significant within-group improvement in Physical Fatigue (Weeks 16, 20, and 24); General Fatigue (Weeks 20 and 24); Mental Fatigue (Week 20); and Reduced Activity (Weeks 20 and 24). These patients also experienced significant within-group improvement in BPI pain, anxiety, depressed mood, bothered by sleep difficulties, and stiffness. Overall, the most common (> 5% incidence) fatigue-related treatment-emergent adverse events were fatigue, somnolence, and insomnia.
Treatment with duloxetine significantly improved multiple dimensions of fatigue in patients with fibromyalgia, and improvement was maintained for up to 24 weeks.
ClinicalTrials.gov registry NCT00673452.
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