Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS), 2020, Barohn

Dolphin · Aug 28, 2020

https://jamanetwork.com/journals/jamaneurology/article-abstract/2769608

Original Investigation
August 17, 2020

Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS)Bayesian Adaptive Comparative Effectiveness Randomized Trial

Richard J. Barohn, MD1; Byron Gajewski, PhD2; Mamatha Pasnoor, MD1; et al Alexandra Brown, MS2; Laura L. Herbelin, BS1; Kim S. Kimminau, PhD3; Dinesh Pal Mudaranthakam, MBA2; Omar Jawdat, MD1; Mazen M. Dimachkie, MD1; and the Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS) Study Team

JAMA Neurol. Published online August 17, 2020. doi:10.1001/jamaneurol.2020.2590
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Key Points
Question Which of the most commonly prescribed medications (pregabalin, duloxetine, nortriptyline, and mexiletine) is best tolerated and most effective for reducing pain in patients with cryptogenic sensory polyneuropathy?

Findings In a bayesian adaptive randomized clinical trial including 402 patients with cryptogenic sensory polyneuropathy, none of the 4 drugs were clearly superior in performance. However, nortriptyline and duloxetine performed better than pregabalin and mexiletine when efficacy and tolerability were both considered.

Meaning Nortriptyline or duloxetine should be considered first for the treatment of pain among patients with cryptogenic sensory polyneuropathy.
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Abstract
Importance Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers. There are no comparative studies that identify the most effective medication for pain reduction in CSPN.

Objective To determine which medication (pregabalin, duloxetine, nortriptyline, or mexiletine) is most effective for reducing neuropathic pain and best tolerated in patients with CSPN.

Design, Setting, and Participants From December 1, 2014, through October 20, 2017, a bayesian adaptive, open-label randomized clinical comparative effectiveness study of pain in 402 participants with CSPN was conducted at 40 neurology care clinics. The trial included response adaptive randomization. Participants were patients with CSPN who were 30 years or older, with a pain score of 4 or greater on a numerical rating scale (range, 0-10, with higher scores indicating a higher level of pain). Participant allocation to 1 of 4 drug groups used the utility function and treatment’s sample size for response adaptation randomization. At each interim analysis, a decision was made to continue enrolling (up to 400 participants) or stop the whole trial for success (80% power). Patient engagement was maintained throughout the trial, which helped guide the study and identify ways to communicate and disseminate information. Analysis was performed from December 11, 2015, to January 19, 2018.

Interventions Participants were randomized to receive nortriptyline (n = 134), duloxetine (n = 126), pregabalin (n = 73), or mexiletine (n = 69).

Main Outcomes and Measures The primary outcome was a utility function that was a composite of the efficacy (participant reported pain reduction of ≥50% from baseline to week 12) and quit (participants who discontinued medication) rates.

Results Among the 402 participants (213 men [53.0%]; mean [SD] age, 60.1 [13.4] years; 343 White [85.3%]), the utility function of nortriptyline was 0.81 (95% bayesian credible interval [CrI], 0.69-0.93; 34 of 134 [25.4%] efficacious; and 51 of 134 [38.1%] quit), of duloxetine was 0.80 (95% CrI, 0.68-0.92; 29 of 126 [23.0%] efficacious; and 47 of 126 [37.3%] quit), pregabalin was 0.69 (95% CrI, 0.55-0.84; 11 of 73 [15.1%] efficacious; and 31 of 73 [42.5%] quit), and mexiletine was 0.58 (95% CrI, 0.42-0.75; 14 of 69 [20.3%] efficacious; and 40 of 69 [58.0%] quit). The probability each medication yielded the highest utility was 0.52 for nortriptyline, 0.43 for duloxetine, 0.05 for pregabalin, and 0.00 for mexiletine.

Conclusions and Relevance This study found that, although there was no clearly superior medication, nortriptyline and duloxetine outperformed pregabalin and mexiletine when pain reduction and undesirable adverse effects are combined to a single end point.

Trial Registration ClinicalTrials.gov Identifier: NCT02260388
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Snow Leopard · Aug 28, 2020

Open-label...

Arnie Pye · Aug 28, 2020

I wonder how many of the participants in this trial were tested for vitamin B6 deficiency. It causes neuropathy, several other symptoms, and can even cause seizures. It's also simple to fix.

Vitamin B6 Deficiency and Dependency

rvallee · Aug 28, 2020

The "patient engagement" looks like tokenism. Exactly like how Chalder and Crawley abuse it.

It puts the lotion on its skin or else it gets the hose again is not an actual choice.

Arnie Pye · Aug 28, 2020

rvallee said: ↑

It puts the lotion on its skin or else it gets the hose again is not an actual choice.
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https://www.youtube.com/watch?v=9ToNZHG5KHw

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Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS), 2020, Barohn

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