Prediction of treatment response to capsaicin 8% patch: Lessons to be learned from daily clinical practice
Caspar Skau Madsen, Nanna Brix Finnerup published online 06 June 2013.
In this issue of the Scandinavian Journal of Pain, Gustorff et al. have carefully examined neuropathic pain patients treated with the capsaicin 8% patch and have identified possible predictors for treatment response [1].
Neuropathic pain is often a chronic disabling condition. First-line analgesic treatments include antidepressants and gabapentin or pregabalin, but treatment often provides only partial relief or may be associated with intolerable side effects[2]. Randomized controlled trials (RCTs) have shown that patients tend to have either minimal pain relief or very good pain relief from a given drug. Unfortunately, RCTs rarely include characterizations of patients who respond to the treatment, and thus little is known about the predictors of response to various treatments. As a consequence, treatment continues to be a trial-and-error process.
In the past 10 years, different topical treatments for peripheral neuropathic pain have been introduced. The most important treatment options are lidocaine and capsaicin patches and also intradermal injections of botulinum toxin type A. Qutenza, a cutaneous patch of capsaicin 8%, has been given marketing authorization in Europe with the indication: “treatment of peripheral neuropathic pain in non-diabetic adults” and FDA approval for postherpetic neuralgia. Capsaicin 8% patches are applied to the pain area for 30 or 60
minutes, and the treatment can be repeated after 3 months. This is usually done in a hospital setting. The first studies on the high-concentration capsaicin path (NGX-4010) emerged in 2008 [3], [4]. Subsequent studies have confirmed the effect of high-dose capsaicin in postherpetic neuralgia, but one study failed to reproduce the positive findings in HIV neuropathy [5]. No published RCTs have tested the capsaicin 8% patch in other neuropathic pain conditions. Since the application of the capsaicin 8% patch is painful, a low-dose capsaicin application has been used as an active control to ensure blinding in RCTs. The treatment is generally well tolerated and apart from the pain experienced during the application, it has limited side effects, although little is still known about the long-term effect and safety of repeated applications.
The effect of the capsaicin 8% patch is modest, but as for other analgesic treatments some patients seem to obtain a good effect, while other patients fail to respond, and it would be extremely valuable to be able to predict the treatment response. Gustorff and colleagues are to be congratulated for having systematically assessed the patients before the treatment with the capsaicin 8% patch and examined factors related to treatment response. In this observational study, 57 patients with postherpetic neuralgia, peripheral nerve injury or polyneuropathy were carefully assessed with quantitative sensory testing before treatment with capsaicin 8% patches. Patients with ≥30% pain reduction by day 7/10 were classified as responders. The etiology of the neuropathic pain did not predict the response to treatment, but there was one variable in the quantitative sensory testing that predicted response. Perhaps surprisingly, non-responders had significantly worse dynamic mechanical allodynia at baseline than responders. We can only speculate on the mechanisms underlying the neuropathic pain in patients with allodynia and the lack of effect of capsaicin patches, but it provides useful information for the clinical treatment of neuropathic pain patients.
Is this result from a non-placebo controlled exploratory observational study useful, considering the sometimes very large placebo responses in pain treatment? Yes, it is. The hypothesis generated from this careful examination of patients will of course need to be tested in an RCT, but at least now we have a hypothesis. Maybe of even more importance, the knowledge that allodynia may predict non-response to the capsaicin 8% patch will hopefully prevent researchers from including only patients with allodynia in their trials, which is the case in some RCTs, although rarely justified.
References
3. Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan P, Rauck R, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7:1106–1112
4. Simpson DM, Brown S, Tobias J. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology. 2008;70:2305–2313
5. Clifford DB, Simpson DM, Brown S, Moyle G, Brew BJ, Conway B, et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. J Acquir Immune Defic Syndr. 2012;59:126–133
Neuropathic pain is often a chronic disabling condition. First-line analgesic treatments include antidepressants and gabapentin or pregabalin, but treatment often provides only partial relief or may be associated with intolerable side effects[2]. Randomized controlled trials (RCTs) have shown that patients tend to have either minimal pain relief or very good pain relief from a given drug. Unfortunately, RCTs rarely include characterizations of patients who respond to the treatment, and thus little is known about the predictors of response to various treatments. As a consequence, treatment continues to be a trial-and-error process.
In the past 10 years, different topical treatments for peripheral neuropathic pain have been introduced. The most important treatment options are lidocaine and capsaicin patches and also intradermal injections of botulinum toxin type A. Qutenza, a cutaneous patch of capsaicin 8%, has been given marketing authorization in Europe with the indication: “treatment of peripheral neuropathic pain in non-diabetic adults” and FDA approval for postherpetic neuralgia. Capsaicin 8% patches are applied to the pain area for 30 or 60
minutes, and the treatment can be repeated after 3 months. This is usually done in a hospital setting. The first studies on the high-concentration capsaicin path (NGX-4010) emerged in 2008 [3], [4]. Subsequent studies have confirmed the effect of high-dose capsaicin in postherpetic neuralgia, but one study failed to reproduce the positive findings in HIV neuropathy [5]. No published RCTs have tested the capsaicin 8% patch in other neuropathic pain conditions. Since the application of the capsaicin 8% patch is painful, a low-dose capsaicin application has been used as an active control to ensure blinding in RCTs. The treatment is generally well tolerated and apart from the pain experienced during the application, it has limited side effects, although little is still known about the long-term effect and safety of repeated applications.The effect of the capsaicin 8% patch is modest, but as for other analgesic treatments some patients seem to obtain a good effect, while other patients fail to respond, and it would be extremely valuable to be able to predict the treatment response. Gustorff and colleagues are to be congratulated for having systematically assessed the patients before the treatment with the capsaicin 8% patch and examined factors related to treatment response. In this observational study, 57 patients with postherpetic neuralgia, peripheral nerve injury or polyneuropathy were carefully assessed with quantitative sensory testing before treatment with capsaicin 8% patches. Patients with ≥30% pain reduction by day 7/10 were classified as responders. The etiology of the neuropathic pain did not predict the response to treatment, but there was one variable in the quantitative sensory testing that predicted response. Perhaps surprisingly, non-responders had significantly worse dynamic mechanical allodynia at baseline than responders. We can only speculate on the mechanisms underlying the neuropathic pain in patients with allodynia and the lack of effect of capsaicin patches, but it provides useful information for the clinical treatment of neuropathic pain patients.
Is this result from a non-placebo controlled exploratory observational study useful, considering the sometimes very large placebo responses in pain treatment? Yes, it is. The hypothesis generated from this careful examination of patients will of course need to be tested in an RCT, but at least now we have a hypothesis. Maybe of even more importance, the knowledge that allodynia may predict non-response to the capsaicin 8% patch will hopefully prevent researchers from including only patients with allodynia in their trials, which is the case in some RCTs, although rarely justified.
References
- Gustorff B, Poole C, Kloimstein H, Hacker N, Likar R. Treatment of neuropathic pain with the capsaicin 8% patch: using quantitative sensory testing to investigate predictors of response to treatment. Scand J Pain. 2013;4:138–145
- 2. Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132:237–251
3. Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan P, Rauck R, et al. NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol. 2008;7:1106–1112
4. Simpson DM, Brown S, Tobias J. Controlled trial of high-concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology. 2008;70:2305–2313
5. Clifford DB, Simpson DM, Brown S, Moyle G, Brew BJ, Conway B, et al. A randomized, double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy. J Acquir Immune Defic Syndr. 2012;59:126–133
http://www.scandinavianjournalpain.com/article/S1877-8860(13)00043-8/fulltext
No comments:
Post a Comment
All comments welcome but advertising your own service or product will unfortunately result in your comment not being published.