Abstract and Introduction
Abstract
Objectives. Meta-analysis of pregabalin trials in FM using company trial reports, which provide more detailed information about trials than published papers. FM is a common condition with a significant impact on quality of life.
Methods. Reports of five high-quality randomized trials (3808 patients) of pregabalin in FM were obtained from Pfizer. Four trials (2754 patients) were of classical trial design and one was an enriched enrolment randomized withdrawal design. Outcomes for meta-analysis from the four trials with classical design were pooled in an intention-to-treat analysis.
Results. Significant benefit of pregabalin over placebo was seen for a variety of outcomes including mean pain and sleep scores, the proportion of patients achieving at least 50% pain relief and most of the individual domains of short-form 36. Only a minority of patients achieve moderate or substantial pain relief. The proportions of patients with any adverse event, somnolence or dizziness were also significantly greater with pregabalin than with placebo. There was no difference with regard to serious adverse events. A dose–response relationship was apparent for at least 50% pain relief and for adverse event outcomes.
Conclusions. Pregabalin is effective in treating FM and is relatively safe. The size of therapeutic effect is similar to that with other recent interventions such as duloxetine and the combination of tramadol and paracetamol. Enriched enrolment randomized withdrawal design gives similar results to classical trial designs in FM.
Introduction
FM is surrounded by controversy regarding both its aetiology and its status as a disease entity. Preliminary genetic and neurobiological evidence exists supporting differences between FM patients and controls extending beyond subjective patient reports of pain and interference with daily living. Candidate biomarkers that may help to identify susceptible individuals or parallel disease activity are emerging.
FM is defined as widespread pain for >3 months with pain on palpation at 11 or more of 18 specified tender points. There are often other symptoms, such as poor sleep, fatigue and depression.
FM profoundly limits activities of daily living, comparable with extent to RA, and has a considerable effect on productivity. It is common, especially in women, with an all-age prevalence of 1–2%. The female to male ratio is 6:1.
No current pharmacological or non-pharmacological FM treatment is entirely satisfactory, with most of them producing moderate or substantial pain relief in a minority only. With 60/120 mg duloxetine, with the largest numbers of patients before pregabalin trials, only 37% had a substantial benefit of at least 50% pain relief.
Pregabalin shares with gabapentin a novel high-affinity drug binding site, the calcium channel alpha2-delta subunit, and was the first drug to be licensed by the FDA for FM. The use of pregabalin in FM has been assessed in five clinical trials. Based on these trials this article performs a meta-analysis with regard to efficacy and safety outcomes.