Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial.

Neuropathic pain and spasticity after spinal cord injury (SCI) represent significant problems. Palmitoylethanolamide (PEA), a fatty acid amide that is produced in many cells in the body, is thought to potentiate the action of endocannabinoids and to reduce pain and inflammation. This randomized, double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. A pain diary was completed and questionnaires were completed before and after the 12-week treatment with either placebo or PEA-um. The primary outcome measure was the change in mean neuropathic pain intensity from the 1-week baseline period to the last week of treatment measured on a numeric rating scale ranging from 0 to 10. The primary efficacy analysis was the intention to treat (baseline observation carried forward). Secondary outcomes included a per protocol analysis and effects on spasticity, evoked pain, sleep problems, anxiety, depression, and global impression of change. We randomized 73 individuals with neuropathic pain due to SCI, of which 5 had a major protocol violation, and thus 68 were included in the primary analysis. There was no difference in mean pain intensity between PEA-um and placebo treatment (P = 0.46, mean reductions in pain scores 0.4 (-0.1 to 0.9) vs 0.7 (0.2-1.2); difference of means 0.3 (-0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity, insomnia, or psychological functioning. PEA was not associated with more adverse effects than placebo.

Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor?

OBJECTIVE: To investigate the efficacy of switching to a second biological drug in rheumatoid arthritis (RA) patients. METHODS: Since 2000, Danish RA patients (n = 1021) receiving biological therapy have been registered in the nationwide DANBIO database. The first and second treatment series of patients, who switched therapy before 2005 (n = 235), were analysed for their reasons for switching, Disease Activity Score 28 (DAS28), DAS28 improvement, European League against Rheumatology (EULAR) response and drug survival. Most patients switched from infliximab to etanercept or adalimumab. RESULTS: Median survivals for switchers' first/second treatment were 37/92 weeks (all patients' first treatment 119 weeks). Reasons for switching were lack of efficacy (LOE; 109 patients), adverse events (AE; 72), other reasons (54). If patients experienced AE to the first drug, 15% had AE to the second. Median DAS28 improvements in first/second treatment at 3 months were: LOE switchers 1.1/1.6; AE switchers 1.5/0.8. In LOE switchers, a good/moderate EULAR response was more prevalent during the second treatment course than during the first (63% versus 54%, p = 0.02). AE switchers achieved similar EULAR responses to both treatments (59% versus 50%, p = 0.38). CONCLUSION: LOE switchers had a better clinical response to the second treatment. AE switchers responded equally well to both treatments, with a low risk of discontinuing the second drug as a result of AE. Drug survival of the switchers' second biological therapy was higher than of the first, but lower than that of non-switchers. No difference between various sequences of drugs were found. Danish post-marketing data thus support that RA patients may benefit from switching biological therapy.