by Elena Moro
For September 2017, we have selected: Hoffman EM, Watson JC, St Sauver J, Staff NP, Klein CJ. Association of long-term opioid therapy with functional status, adverse outcomes, and mortality among patients with polyneuropathy. JAMA Neurology 2017;74:773-779.
Neuropathic pain is a common symptom in polyneuropathy that can be difficult to manage. Opioids are usually recommended as second-line treatment, with primary care physicians being mainly involved in opioid prescription. Little is available concerning the long-term outcome (longer than 90 days) of opioids treatment in patients with polyneuropathy.
In this retrospective population-based cohort study conducted in Olmsted County, Minnesota in the US, the authors analyzed the prevalence of long-term (≥ 90 continuous days) opioids therapy in neuropathic patients compared to matched controls, the association between treatment duration and functional status, the adverse events, and mortality. The Rochester Epidemiology Project (REP) database was used to identify patients and controls, as well as a comprehensive prescription database to find details about opioid prescriptions.
From January 2006 to November 2016, 2892 patients with polyneuropathy (mean [SD] age, 67.5 [16.6] years) were identified and compared with 14435 controls (mean [SD] age, 67.5 [16.5] years). About 50.6% of patients (1464) received opioids for less than 90 days, and 18.8% (545) the long-term therapy. Compared to controls (5.4%, 780), the long-term opioids use was significantly higher in polyneuropathy patients (OR 2.4; 95% CI, 2.2-2.8). Moreover, female patients were significantly using more long-term treatment compared to male patients (p <0.001). Long-term opioid treatment was significantly associated with higher comorbidities (Charlson Comorbidity Index comorbidities). Oxycodone was the most common prescribed opioid.
Opioids prescribing physicians were mainly internal medicine (69.5%) and to a lesser extent family medicine (13.2%) doctors. The main indication for opioids was musculoskeletal pain in 52.5% of the polyneuropathy patients (282) whereas polyneuropathy was the indication for only (24%)129 patients with polyneuropathy. The long-term opioid therapy was associated with having pain at the end of the treatment compared with patients with short-term therapy (OR, 2.5;95%, 1.9-3.4). Moreover, there was a significant worsening of activities of daily living and more self-reported functional limitations such as difficulty in climbing stairs (OR, 1.7;95% CI, 1.2-2.4) or being unable to work (OR, 1.3; 95% CI, 0.8-2.0) at the end of the study period with long-term opioids therapy in polyneuropathy patients. More adverse outcomes were found in polyneuropathy patients with long-term opioid therapy, such as depression, opioid overdose and dependence, and other chemical dependence.
“This study shows that opioids long-term treatment in patients with polyneuropathy is not only unsatisfactory but it can also be hazardous and thus should be left in the hands of experienced neurologists or pain specialists”, says Prof. Giorgio Cruccu, Department of Neurology and Psychiatry, Sapienza University, Rome, Italy, EAN Scientific Panel on Pain. “Chronic treatment was associated with no pain improvement at the end of therapy, worsened functional outcome and more adverse events. The study is interesting, since it provides epidemiological data from a very large cohort of patients with the historical reliability of the neuropathy Rochester centre. However, it fails on a crucial aspect. It does not compare severity of polineuropathy, intensity or quality of pain, or functional performance at baseline. Hence, the results may be simply due to the patients prescribed with long-term opioid treatment being those with a more severe disease, as it is often the case in clinical practice. These patients are bound to worsen over time in their sensory and motor functions independently from a non-disease-modifying treatment. No surprise that they did so poorly in climbing stairs or developed depression. Furthermore, nothwistanding the increased risks of opioid abuse and dependence were actually far lower than what most physician would expect, this article gives the message that long-term opioid treatment does not bring advantages, it is only dangerous. This is a dogma in the anti-opioid treatment campaign that is currently growing in the US. This is not the case in EU. In our meta-analysis on pharmacological treatment of painful neuropathy, opioids were the most efficacious drug class in relieving neuropathic pain. When I deal with patients that barely benefit a little bit from antidepressants plus gabapentinoids, I would feel miserable to deny them anything that can alleviate their pain and helps them to get along, even though I am aware I cannot change their course of disease.
“Interestingly, neurologists and pain clinicians were minimally involved in opioids prescriptions, which conducted to opioids dependence in 7.2% of polyneuropathy patients and overdose in 2.6%,” says Prof. Marianne de Visser, Department of Neurology, Amsterdam, The Netherlands. “Moreover, opioids were prescribed mostly for musculoskeletal pain rather than for neuropathic symptoms. Taking together, these findings support the need of multidisciplinary approach and careful counseling when considering chronic opioids therapy in patients with polyneuropathy.”
The other nominees for the September 2017 paper of the month are:
- Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med 2017;377:317-28. A sustained remission after one-year treatment with the interleukin-6 receptor alpha inhibitor tocilizumab (combined with a 26-week prednisone taper) was found in patients with giant-cell arteritis. The difference was significant compared to placebo (combined with prednisone taper over a period of 26 weeks or 52 weeks). Tocilizumab was well tolerated.
- Moresoli P, Habib B, Revnier P, Secrest MH, Eisenberg MJ, Filion KB. Carotid stenting versus endoarterectomy for asymptomatic carotid artery stenosis. A systematic review and meta-analysis. Stroke 2017;48:2150-2157. Results coming from 5 randomized controlled trials including 3019 asymptomatic patients show that there was no significant difference in terms of efficacy between carotid artery stenting (CAS) and carotid endoarteriectomy (CEA). However, there was a trend towards higher risk of periprocedural stroke or death with CAS.
- Pollack CV, Reilly PA, van Ryn J, et al. Idarucizumab for dabigatran reversal – Full cohort analysis. N Engl J Med 2017, July 11. DOI: 10.1056/NEJMoa1707278. In this multicenter, prospective, open-label study, 503 patients who had uncontrolled bleeding or were about to undergo an urgent procedure were enrolled to test the efficacy of idarucizumab in reversing the anticoagulant effect of dabigatan. Idarucizumab could reverse up to 100% the effect of dabigatan within 4 hours. Uncontrolled bleeding was on average stopped within 2.5 hours.
- Chan D, Binks S, Nicholas JM, et al. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet Neurol 2017; 16: 591–600. The secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with secondary progressive multiple sclerosis randomly assigned to either 80 mg simvastatin or placebo, supports the positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure.