genotype can help to predict effectiveness and safety during opioid treatment for chronic low back pain: results from a retrospective study in an Italian cohort.

BACKGROUND

Opioids are widely used for chronic low back pain (CLBP); however, it is still unclear how to predict their effectiveness and safety. Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity.

PURPOSE

genetic polymorphisms could potentially help to predict the effectiveness and safety of opioid-based drugs in clinical practice, especially in the treatment of CLBP.

PATIENTS AND METHODS

A cohort of 224 Italian patients with CLBP treated with codeine or oxycodone was retrospectively evaluated to determine whether adverse reactions and effectiveness were related to single-nucleotide polymorphisms. genotyping was performed using the xTAG CYP2D6 Kit v3 (Luminex) to determine metabolizer phenotype (poor, intermediate, rapid and ultrarapid). Subjects from the cohort were categorized into two groups according to the occurrence of side effects (Case) or benefit (Control) after chronic analgesic treatment. The impact of polymorphism on treatment outcome was tested at the metabolizer phenotype, diplotype and haplotype levels.

RESULTS

polymorphism was significantly associated with opioid treatment outcome (Omnibus =0.018, for both global haplotype and diplotype distribution test). *6 and *9 carriers, alleles characterized by a reduced (*9) or absent (*6) enzymatic activity, were significantly (<0.05) associated with therapeutic failure. ultrarapid metabolizers (*2N patients) showed an increased risk of side effects, as would be predicted. Despite their low frequency, *1/*11, *4/*6 and 41/ 2N diplotypes showed significant (<0.05) associations of efficacy and side effects with chronic opioid treatment.

CONCLUSION

Our results showed that reduced CYP2D6 activity is correlated with lack of therapeutic effect. We found that the pharmacogenetic analysis of could be helpful in foreseeing the safety and effectiveness of codeine or oxycodone treatment in CLBP.