Systematic review of tapentadol in chronic severe pain.

AIM: A systematic review of chronic pain treatment with strong opioids (step 3 WHO pain ladder) and a comparison to a new drug recently approved for the treatment of severe chronic pain in Europe, tapentadol (Palexia, Nucynta*), were performed. METHODS: Thirteen electronic databases were searched as well as a number of other sources from 1980 up to November 2010 for relevant randomized controlled clinical trials in chronic moderate and severe pain investigating at least one step 3 opioid. Chronic pain could be nociceptive or neuropathic, malignant or non-malignant, all systemic administrations were considered as well as trials of different lengths. Two separate analyses were performed, one only for trials which reported (at least as sub-groups) the outcome in patients with severe pain, the other including both moderate and severe pain conditions. With the exception of the direct comparison between tapentadol, oxycodone and placebo, indirect comparisons were performed based on a network analysis. Trials with an enriched or an enriched withdrawal design were excluded. Primary (pain intensity) and a number of secondary endpoints were evaluated, including pain relief (30% and 50%), patient global impression of change, quality of life, quality of sleep, discontinuations, as well as serious adverse events and selected adverse events. RESULTS: Only 10 trials were eligible for analysis of patients with severe pain (eight investigating tapentadol and two trials comparing buprenorphine patch vs placebo). For moderate and severe pain, 42 relevant trials were identified and indirect comparisons with transdermal buprenorphine, transdermal fentanyl, hydromorphone, morphine, and oxymorphone were performed. This report focuses on the network analysis. Tapentadol showed statistically favourable results over oxycodone for pain intensity, 30% and 50% pain relief, patient global impression of change (PGIC), and quality of life. Furthermore, some of the most important adverse events of chronic opioid treatment were significantly less frequent with tapentadol as compared to oxycodone, i.e. constipation, nausea, and vomiting; discontinuations due to these adverse events were found significantly reduced with tapentadol. Similar results were obtained for the network analysis, i.e. tapentadol was superior for the primary outcome (pain intensity) to hydromorphone and morphine, whereas fentanyl and oxymorphone showed trends in favour of these treatments. Significantly less frequent gastrointestinal adverse events of tapentadol were observed in comparison with fentanyl, hydromorphone, morphine, and oxymorphone, apparently leading to significantly reduced treatment discontinuations (for any reason). CONCLUSIONS: Taken together, the benefit-risk ratio of tapentadol appears to be improved compared to step 3 opioids.

Biological response genes after single dose administration of interferon beta-1b to healthy male volunteers.

Treatment with interferon beta-1b (IFNB-1b) is clinically effective in multiple sclerosis patients. However, the mechanism of action is only partially understood, and validated biological response markers are lacking. We assessed IFNB-1b-induced transcriptional changes by microarray technology. Healthy male volunteers received 250 mug IFNB-1b or placebo in a double-blind, randomized controlled trial (n=5 per group). Most transcripts demonstrated peak levels after 6-12 h and returned to baseline after 48 h. We identified 227 differentially regulated genes including novel and previously described markers. This panel may become a valuable tool for development of new IFNB-1b formulations and assessment of clinical drug effects.

Increased expression of Wnt5a in psoriatic plaques.

Psoriasis vulgaris is characterized by hyperproliferation and incomplete terminal differentiation of epidermal keratinocytes. Despite the established role of Wnt pathways in the regulation of stem cell proliferation and differentiation, they have not yet been associated with the pathophysiology of psoriasis. Here, we took biopsies from uninvolved and from lesional skin of 20 patients with plaque-type psoriasis. The biopsies were used for microarray RNA expression profiling. Based on paired samples from 13 patients, we defined 179 genes that were more than 2-fold differentially expressed in lesional skin. This list included 16 genes with known or possible association to the canonical Wnt/beta-catenin or the non-canonical Wnt/Ca2+ pathway. The expression of Wnt5a was 4-fold higher in lesional skin. Other Wnt molecules were largely unchanged (Wnt4 and Wnt16), or tended to be expressed at lower levels (Wnt7b). The mRNA expression levels of two inhibitory factors related to Wnt signaling, frizzled-related protein, and dickkopf homolog 2, were reduced in lesional skin, as was mRNA expression of cyclin D1. These findings were confirmed by quantitative reverse transcription-PCR experiments. We conclude that Wnt5a and other Wnt pathway genes are differentially expressed in psoriatic plaques. Their functional contribution to the pathophysiology of psoriasis needs to be elaborated.