TY - JOUR
T1 - Lacosamide in patients with Na(v)1.7 mutations-related small fibre neuropathy
T2 - a randomized controlled trial
AU - de Greef, Bianca T. A.
AU - Hoeijmakers, Janneke G. J.
AU - Geerts, Margot
AU - Oakes, Mike
AU - Church, Tim J. E.
AU - Waxman, Stephen G.
AU - Dib-Hajj, Sulayman D.
AU - Faber, Catharina G.
AU - Merkies, Ingemar S. J.
N1 - Funding Information:
B.T.A.dG. reports a grant from Prinses Beatrix Spierfonds (W.OR12-01), during the conduct of the study. J.G.J.H reports personal fees from Pfizer inc. (travel funding and speakers’ honorarium), and a grant from Prinses Beatrix Spierfonds (W.OK17-09), outside the submitted work. M.G. has nothing to disclose. M.O. reports personal fees from Convergence Pharmaceuticals Limited, during the conduct of the study. T.J.E.C. reports personal fees from Paramstat Ltd, during the conduct of the study. S.G.W. reports personal fees from Amgen, personal fees from Biogen, personal fees from Chromocell, personal fees from SiteOne Therapeutics, outside the submitted work. S.D.D-H. reports personal fees from Gerson Lehrman Group (GLG), outside the submitted work. C.G.F. reports grants from European Union’s Horizon 2020 research and innovation programme Marie Sklodowska-Curie grant for PAIN-Net, Molecule-to-man pain network (grant no. 721841), from European Union 7th Framework Programme (grant n°602273) for the PROPANE study, from Prinses Beatrix Spierfonds (W.OR12-01, W.OR15-25), from Grifols and Lamepro for a trial on IVIg in small fibre neuropathy, and participates in Steering com-mitttees/advisory boards for studies in small fibre neuropathy of Biogen/Convergence, Vertex and Chromocell, outside the submitted work. I.S.J.M. received funding for research from the Talecris Talents program, the GSB CIDP Foundation International, Princes Beatrix foundation, and from the European Union 7th Framework Programme (grant n°602273). Furthermore, a research foundation at the University of Maastricht received honoraria on behalf of him for participation in steering committees of the Talecris ICE Study, LFB, CSL Behring, Novartis, Grifols, and Octapharma. He serves on the editorial board of the Journal of Peripheral Nervous system, is a member of the Inflammatory Neuropathy Consortium (INC), and member of the Peripheral Nerve Society.
Publisher Copyright:
© The Author(s) (2019).
PY - 2019/2
Y1 - 2019/2
N2 - Symptomatic treatment of neuropathic pain in small fibre neuropathy is often disappointing. The finding of voltage-gated sodium channel mutations in small fibre neuropathy (with mutations in SCN9A, encoding for Na(v)1.7) being most frequently reported suggest a specific target for therapy. The anticonvulsant lacosamide acts on Na(v)1.3, Na(v)1.7, and Na(v)1.8. The aim of this study was to evaluate the efficacy, safety, and tolerability of lacosamide as a potential treatment for pain in Na(v)1.7-related small fibre neuropathy. The Lacosamide-Efficacy-'N'-Safety in SFN (LENSS) was a randomized, placebo-controlled, double-blind, crossover-design study. Subjects were recruited in the Netherlands between November 2014 and July 2016. Patients with Na(v)1.7-related small fibre neuropathy were randomized to start with lacosamide followed by placebo or vice versa. In both 8-week treatment phases, patients received 200 mg two times a day (BID), preceded by a titration period, and ended by a tapering period. The primary outcome was efficacy, defined as the proportion of patients with 1-point average pain score reduction compared to baseline using the Pain Intensity Numerical Rating Scale. The trial is registered with ClinicalTrials.gov, number NCT01911975. Twenty-four subjects received lacosamide, and 23 received placebo. In 58.3% of patients receiving lacosamide, mean average pain decreased by at least 1 point, compared to 21.7% in the placebo group [sensitivity analyses, odds ratio 5.65 (95% confidence interval: 1.83-17.41); P = 0.0045]. In the lacosamide group, 33.3% reported that their general condition improved versus 4.3% in the placebo group (P-value = 0.0156). Additionally, a significant decrease in daily sleep interference, and in surface pain intensity was demonstrated. No significant changes in quality of life or autonomic symptoms were found. Lacosamide was well tolerated and safe in use. This study shows that lacosamide has a significant effect on pain, general wellbeing, and sleep quality. Lacosamide was well tolerated and safe, suggesting that it can be used for pain treatment in Na(v)1.7-related small fibre neuropathy.
AB - Symptomatic treatment of neuropathic pain in small fibre neuropathy is often disappointing. The finding of voltage-gated sodium channel mutations in small fibre neuropathy (with mutations in SCN9A, encoding for Na(v)1.7) being most frequently reported suggest a specific target for therapy. The anticonvulsant lacosamide acts on Na(v)1.3, Na(v)1.7, and Na(v)1.8. The aim of this study was to evaluate the efficacy, safety, and tolerability of lacosamide as a potential treatment for pain in Na(v)1.7-related small fibre neuropathy. The Lacosamide-Efficacy-'N'-Safety in SFN (LENSS) was a randomized, placebo-controlled, double-blind, crossover-design study. Subjects were recruited in the Netherlands between November 2014 and July 2016. Patients with Na(v)1.7-related small fibre neuropathy were randomized to start with lacosamide followed by placebo or vice versa. In both 8-week treatment phases, patients received 200 mg two times a day (BID), preceded by a titration period, and ended by a tapering period. The primary outcome was efficacy, defined as the proportion of patients with 1-point average pain score reduction compared to baseline using the Pain Intensity Numerical Rating Scale. The trial is registered with ClinicalTrials.gov, number NCT01911975. Twenty-four subjects received lacosamide, and 23 received placebo. In 58.3% of patients receiving lacosamide, mean average pain decreased by at least 1 point, compared to 21.7% in the placebo group [sensitivity analyses, odds ratio 5.65 (95% confidence interval: 1.83-17.41); P = 0.0045]. In the lacosamide group, 33.3% reported that their general condition improved versus 4.3% in the placebo group (P-value = 0.0156). Additionally, a significant decrease in daily sleep interference, and in surface pain intensity was demonstrated. No significant changes in quality of life or autonomic symptoms were found. Lacosamide was well tolerated and safe in use. This study shows that lacosamide has a significant effect on pain, general wellbeing, and sleep quality. Lacosamide was well tolerated and safe, suggesting that it can be used for pain treatment in Na(v)1.7-related small fibre neuropathy.
KW - small fibre neuropathy
KW - lacosamide
KW - Na(v)1
KW - 7 mutations
KW - neuropathic pain
KW - RCT
KW - SODIUM-CHANNELS
KW - SLOW-INACTIVATION
KW - DOUBLE-BLIND
KW - PAIN
KW - EFFICACY
KW - SAFETY
KW - PATHOPHYSIOLOGY
KW - CRMP2
U2 - 10.1093/brain/awy329
DO - 10.1093/brain/awy329
M3 - Article
C2 - 30649227
SN - 0006-8950
VL - 142
SP - 263
EP - 275
JO - Brain
JF - Brain
ER -