We thank Drs. Schwartz, Urits and Viswanath for their comment, and we feel honored by their appraisal of our study. (Low) back pain treatment can be demanding, and we agree that systemic analgesics (including non-steroidal anti-inflammatory drugs [NSAIDs] and opioids) can play a role in the treatment of (low) back pain, but they do have their limitations in terms of efficacy, as well as tolerability and safety.
Topical NSAIDs might be treatment options; however, the database on efficacy for (low) back pain is rather limited. Neither the British National Institute for Health and Care Excellence (NICE) guideline [1] nor the US guideline [2] even mention topical NSAIDs, and the German guideline on diagnosis and treatment of non-specific low back pain [3] does not recommend these treatments due to the lack of clinical data.
The results of our study contribute to answering two questions. The first is: Is topical diclofenac more effective than placebo? In our study, the effect was similar to placebo, although an earlier study with another diclofenac formulation using the same methodology showed an effect on neck pain [4]. In this respect, Wiffen and Xia [5] recently highlighted the importance of the pharmaceutical formulation for effective pain relief. The second question is: Is topical capsaicin effective? The answer was yes, and—not surprisingly—the combination of both compounds did not exceed the efficacy of capsaicin alone. As one might imagine, our hope was that the combination treatment would exceed the efficacy of both single compound treatments.
Topical capsaicin (or the structurally similar nonivamide) has a long tradition of being used for the treatment of musculoskeletal pain, including (low) back pain. At least three state-of-the-art double-blind, placebo-controlled, randomized trials have been published in recent years (two of them on a fixed-dose combination of nonivamide with a nicotinic acid ester) showing that this pharmacological approach worked well for low back pain patients [6–8]. In two of these studies, efficacy outcomes approached or exceeded those described for several prescription-only treatments [9].
Thus, topical transient receptor potential vanilloid subunit 1 (TRPV1) receptor agonists like capsaicin can be considered to be a promising addition to the armamentarium of (low) back pain treatments.
Acknowledgements
As the letter to the editor covers the topic of topical versus system analgesics in a much broader sense than the original full trial publication, this reply has been written by TWW and RL as medical representatives of the team.
Funding
No funding or sponsorship was received for the publication of this article.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Disclosures
Thomas W. Weiser and Robert Lange are employees and stock holders of Sanofi.
Compliance with Ethics Guidelines
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
Peer Review
Please note, contrary to the journal’s standard single-blind peer review process, as a letter this article underwent review by a member of the journal’s Editorial Board.
Footnotes
Digital Features To view digital features for this article go to 10.6084/m9.figshare.12505706.
References
- 1.Bernstein IA, Malik Q, Carville S, Ward S. Low back pain and sciatica: summary of NICE guidance. BMJ. 2017;356:i6748. doi: 10.1136/bmj.i6748. [DOI] [PubMed] [Google Scholar]
- 2.Qaseem A, Wilt TJ, McLean RM, Forciea MA. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American college of physicians. Ann Intern Med. 2017;166(7):514–530. doi: 10.7326/M16-2367. [DOI] [PubMed] [Google Scholar]
- 3.Clinical practice guideline: Non-specific low back pain. https://www.leitlinien.de/nvl/html/kreuzschmerz/kapitel-1. Accessed 22 May 2020
- 4.Predel HG, Giannetti B, Pabst H, Schaefer A, Hug AM, Burnett I. Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study. BMC Musculoskelet Disord. 2013;14:250. doi: 10.1186/1471-2474-14-250. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Wiffen X. Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain. Curr Med Res Opin. 2020;36(4):637–650. doi: 10.1080/03007995.2020.1716703. [DOI] [PubMed] [Google Scholar]
- 6.Chrubasik S, Weiser T, Beime B. Effectiveness and safety of topical capsaicin cream in the treatment of chronic soft tissue pain. Phytother Res. 2010;24(12):1877–1885. doi: 10.1002/ptr.3335. [DOI] [PubMed] [Google Scholar]
- 7.Gaubitz M, Schiffer T, Holm C, Richter E, Pisternick-Ruf W, Weiser T. Efficacy and safety of nicoboxil/nonivamide ointment for the treatment of acute pain in the low back—a randomized, controlled trial. Eur J Pain. 2016;20(2):263–273. doi: 10.1002/ejp.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Blahova Z, Holm JC, Weiser T, Richter E, Trampisch M, Akarachkova E. Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain—a randomized, placebo-controlled trial. J Pain Res. 2016;14(9):1221–1230. doi: 10.2147/JPR.S118329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Keller A, Hayden J, Bombardier C, van Tulder M. Effect sizes of non-surgical treatments of non-specific low-back pain. Eur Spine J. 2007;16(11):1776–1788. doi: 10.1007/s00586-007-0379-x. [DOI] [PMC free article] [PubMed] [Google Scholar]