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Scandinavian Journal of Pain

Official Journal of the Scandinavian Association for the Study of Pain

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The utility/futility of medications for neuropathic pain – an observational study

Stephen Butler
  • Corresponding author
  • University Hospital, Pain Center, ING 79, 2 TR, Uppsala 75185, Sweden
  • Department of Family Medicine and Public Health, Uppsala University, Uppsala, Sweden, Phone: +46 18 6110110, Fax: +46 18 503539
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  • Other articles by this author:
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/ Daniel Eek / Lena Ring / Allen Gordon / Rolf Karlsten
Published Online: 2018-11-08 | DOI: https://doi.org/10.1515/sjpain-2018-0317

Abstract

Background and aims

The RELIEF (Real Life) study by AstraZeneca was designed as an observational study to validate a series of Patient Reported Outcome (PRO) questionnaires in a mixed population of subjects with neuropathic pain (NP) coming from diabetes, neurology and primary care clinics. This article is an analysis of a subset of the information to include the medications used and the effects of pharmacological treatment over 6 months. The RELIEF study was performed during 2010–2013.

Methods

Subjects were recruited from various specialty clinics and one general practice clinic across Canada. The subjects were followed for a total of 2 years with repeated documentation of their status using 10 PROs. A total of 210 of the recruited subjects were entered into the data base and analyzed. Of these, 123 had examination-verified painful diabetic neuropathy (PDN) and 87 had examination-verified post-traumatic neuropathy (PTN). To evaluate the responsiveness of the PROs to change, several time points were included and this study focusses primarily on the first 6 months. Subjects also maintained a diary to document all medications, both for pain and other medical conditions, including all doses, start dates and stop dates, that could be correlated to changes in the PRO parameters.

Results

RELIEF was successful in being able to correlate the validity of the PROs and this data was used for further AstraZeneca Phase 1, 2, and 3 clinical trials of NP. To our surprise, there was very little change in pain and low levels of patient satisfaction with treatment during the trial. Approximately 15% of the subjects reported improvement, 8% worsening of pain, the remainder reported pain unchanged despite the use of multiple medications at multiple doses, alone or in combination with frequent changes of medications and doses over the study. Those taking predominantly NSAIDs (COX-inhibitors) did no worse than those taking the standard recommended medications against NP.

Conclusions

Since this is a real-life study, it reflects the clinical utility of a variety of internationally recommended medications for the treatment of NP. In positive clinical trials of these medications in selected “ideal” subjects, the effects are not overwhelming – 30% are 50% improved on average. This study shows that in the real world the results are not nearly as positive and reflects information from non-published negative clinical trials.

Implications

We still do not have very successful medications for NP. Patients probably differ in many respects from those subjects in clinical trials. This is not to negate the use of recommended medications for NP but an indication that success rates of treatment are likely to be worse than the data coming from those trials published by the pharmaceutical industry.

Keywords: neuropathic pain; real world; drug failure; diabetic neuropathy; posttraumatic neuropathy

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About the article

Received: 2018-10-01

Accepted: 2018-10-01

Published Online: 2018-11-08


Authors’ statements

Research funding: This study was funded entirely by AstraZeneca.

Conflict of interest: Rolf Karlsten and Lena Ring were fully employed by AstraZeneca and Stephen Butler was a consultant for AstraZeneca during the RELIEF study. Daniel EEK was and is still an employee of AstraZeneca.

Informed consent: Obtained.

Ethical approval: The protocol was approved by local ethics committees.


Citation Information: Scandinavian Journal of Pain, 20180317, ISSN (Online) 1877-8879, ISSN (Print) 1877-8860, DOI: https://doi.org/10.1515/sjpain-2018-0317.

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